Akkermansia muciniphila is a bacterium that is commonly found in the human gut microbiota and has been found to have potential health benefits. Recently, a study was conducted to investigate the effects of A. muciniphila supplementation in overweight and obese individuals who are at high risk for metabolic syndrome. The study was a proof-of-concept exploratory study that showed promising results in terms of the safety and efficacy of A. muciniphila supplementation. In this article, we will explore the benefits of A. muciniphila supplementation and its potential as a therapeutic intervention for metabolic disorders.
Metabolic syndrome is a collection of conditions that increase an individual's risk of developing cardiovascular disease, stroke, and type 2 diabetes mellitus. It is characterized by a constellation of comorbidities that include high blood pressure, high blood sugar levels, excess body fat, and abnormal cholesterol levels. Recent studies have shown that the gut microbiota plays a critical role in the development and progression of metabolic disorders. The gut microbiota is composed of trillions of microorganisms that interact with each other and with the host, influencing a wide range of physiological processes, including metabolism, immune function, and gut barrier function.
Akkermansia muciniphila is a Gram-negative bacterium that belongs to the Verrucomicrobia phylum. It is a mucin-degrading bacterium that lives in the mucus layer of the gut and feeds on the host's mucin. A. muciniphila has been found to be negatively correlated with overweight, obesity, untreated type 2 diabetes mellitus, and hypertension. Recent studies have shown that A. muciniphila supplementation can improve insulin resistance and reduce inflammation in animal models. However, until recently, the effects of A. muciniphila supplementation in humans had not been investigated.
The study led by Dr. Patrice D. Cani at the Université catholique de Louvain, Belgium, was a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers. The primary endpoints were safety, tolerability, and metabolic parameters, including insulin resistance, circulating lipids, visceral adiposity, and body mass. Secondary outcomes were gut barrier function and gut microbiota composition. The study showed that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well-tolerated.
Compared to the placebo, pasteurized A. muciniphila improved insulin sensitivity by 28.62% and reduced insulinemia by 34.08%. It also reduced plasma total cholesterol by 8.68%. Pasteurized A. muciniphila supplementation slightly decreased body weight by 2.27 kg, fat mass by 1.37 kg, and hip circumference by 2.63 cm compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected.
The results of this proof-of-concept study (clinical trial no. NCT02637115) show that the intervention was safe and well-tolerated and that supplementation with A. muciniphila improves several metabolic parameters. The study provides promising evidence that A. muciniphila supplementation could be a therapeutic intervention for metabolic disorders such as obesity and type 2 diabetes mellitus.
Building on our previous exploration of how diet, medication, and lifestyle choices intricately shape the gut microbiota, part two of our series delves deeper into this fascinating ecosystem. We will examine the profound effects of exercise on gut health, uncover the complex relationship between dietary habits and gut-related diseases, explore the influence of genetics on microbiota composition, and discuss emerging therapeutic applications.
Physical exercise has been identified as a key determinant in shaping gut microbiota. Studies reveal that individuals engaging in regular physical activity exhibit a more diverse microbial population in their intestines, which is linked to improved gut health and enhanced immune function. This diversity is not just in terms of species but also in their functional roles, contributing positively to the host's health. For instance, professional athletes like rugby players have demonstrated a more diverse gut microbiota compared to non-athletes.
This increased microbial diversity is associated with the promotion of an anti-inflammatory state within the gut. Physical activity fosters the production of short-chain fatty acids (SCFAs) by gut microbes, which have anti-inflammatory effects. This is particularly beneficial in managing conditions related to gut inflammation, showcasing the therapeutic potential of exercise in maintaining a healthy gut microbiota and mitigating disease risks linked to microbial dysbiosis.
Additionally, the influence of exercise on gut microbiota extends across different age groups. In children, physical activity is associated with a healthier and more diverse gut microbiota, emphasising the importance of exercise from a young age for gut health and disease prevention.
Regular physical activity is also associated with lower levels of systemic inflammation, contributing to a balanced gut microbiota and prevention of gut-related disorders. Furthermore, exercise leads to changes in the relative abundance of specific beneficial bacterial species, underscoring the multifaceted impact of physical activity on gut microbiota and overall well-being.
Dietary habits profoundly influence the composition and function of the gut microbiome. A Balanced diet plays a crucial role in maintaining overall health and can significantly impact the risk of various diseases. For instance, the Western diet, characterised by low intake of microbiota-accessible carbohydrates (MACs), has been associated with changes in microbiota composition and functionality, potentially leading to inflammation and immune dysregulation.
Given the profound impact of diet on gut health, various dietary habits have been examined for their influence on the gut microbiota. High-fat diets, for example, have been associated with a decrease in intestinal bacterial diversity, negatively impacting gut health and overall well-being. On the other hand, the intake of non-digestible carbohydrates, particularly dietary fiber, has been shown to play a crucial role in shaping the gut microbiome and influencing health outcomes.
A specific example of the impact of diet on the gut microbiome is the influence of the Western diet, which is low in microbiota-accessible carbohydrates (MACs). Research has shown that this diet can lead to alterations in microbiota composition and functionality, potentially resulting in inflammation and immune dysregulation. This underscores the importance of a balanced diet rich in MACs for promoting a healthy gut microbiome and overall well-being.
Long-term dietary habits also have a significant impact on gut microbial diversity. Traditional populations, for example, showcase different gut microbiomes compared to those in modern societies. The shift in human eating habits over time, particularly during the industrial era, has not necessarily contributed to a more resilient gut microbiome. This emphasizes the need for dietary interventions to alleviate health problems associated with microbiota dysbiosis.
Host genetics play a significant role in determining the composition of the gut microbiota. Research has shown that specific genetic loci can significantly influence the microbiome, highlighting the complex interplay between host genetics and the gut microbial ecosystem [10,13].
Several studies have highlighted the complex relationship between host genetics and the gut microbiome. For instance, a genome-wide association study identified 31 loci affecting the microbiome at a genome-wide significant threshold, providing insights into the genetic factors influencing the gut microbiome [10,13]. Such findings not only provide a deeper understanding of the role of genetics in shaping the microbiome but also emphasize the potential for leveraging this knowledge to develop personalized interventions targeting the gut microbiome.
Moreover, the interplay between host genetics and gut microbiota has been implicated in the pathogenesis of various diseases. For instance, compelling evidence suggests that the gut microbiome may play a causal role in conditions like ulcerative colitis and rheumatoid arthritis. This highlights the intricate relationship between host genetics, gut microbiota composition, and human health and underscores the need for a deeper understanding of this relationship.
The composition of the gut microbiota has significant therapeutic implications. Understanding the influence of diet, medication, lifestyle, and genetics on the gut microbiome can guide the development of targeted interventions to optimize gut health [1,2,3,4].
Physical exercise, for instance, has been shown to increase intestinal microbial diversity, promoting an anti-inflammatory state. Recognizing this, healthcare professionals could leverage exercise as a therapeutic intervention to positively influence the gut microbiota. This approach could be particularly beneficial in managing conditions such as inflammatory bowel disease and obesity, which are associated with gut dysbiosis.
Dietary interventions also represent a promising approach to managing gut health. Given that the Western diet, low in microbiota-accessible carbohydrates (MACs), has been linked to altered microbiota composition and functionality, leading to inflammation and immune dysregulation, dietary strategies that promote a balanced intake of MACs could be beneficial. Such strategies could help mitigate the risk of obesity and inflammatory bowel disease, conditions linked to gut microbiota alterations.
In our previous comprehensive exploration of the gut microbiota, spanning two insightful articles, we have unraveled how diet, medication, lifestyle choices, and genetics intertwine to shape this vital ecosystem within us. From the profound impacts of our daily habits on microbial diversity to the potential of targeted dietary and lifestyle interventions, these discussions have highlighted the critical role of gut microbiota in our overall health and well-being. The conclusion underscores the importance of understanding these complex interactions for developing personalised approaches in healthcare. Integrating insights from both parts of our series makes it evident that a holistic view of gut health, informed by individual characteristics and habits, is key to preventing and managing diseases linked to microbial imbalance. This journey through the world of gut microbiota enlightens us about the intricate connections within our bodies and opens up new avenues for health optimisation and disease prevention.
The gut microbiota, comprising trillions of microbes, forms a complex and dynamic ecosystem that is integral to our health and wellbeing [1,2]. These minute organisms are deeply entrenched in numerous vital body functions, ranging from nutrient digestion to the regulation of our immune responses. They also play a substantial role in mental health, contributing to the emerging field of research in the gut-brain axis.
However, the composition of this intricate microbial community is not static and can be influenced by a multitude of factors. Diet, medication, lifestyle choices, and even genetics can significantly affect the diversity and balance of the gut microbiota [1,3,4]. For instance, a diet rich in fibre can nurture a diverse array of beneficial gut microbes, while long-term medication use can disrupt this balance, leading to a less diverse microbiota [1,3]. Similarly, lifestyle choices such as physical activity levels or sleep patterns can have substantial impacts on gut microbial composition. Even our genetic makeup plays a role in determining which microbial species inhabit our gut microbiome composition. Therefore, understanding these influences is key to harnessing the potential of the gut microbiota in promoting health and preventing disease.
Dietary habits significantly affect the diversity and health of our gut microbiota, with each individual possessing a unique gut microbiota composition principally shaped by long-term dietary habits. Carbohydrates, being the primary source of energy for the human body, have a profound impact on the gut microbiome. Non-digestible carbohydrates, in particular, serve as a crucial fuel source for certain types of beneficial bacteria, promoting their growth and activity. Dietary fibre plays a vital role in maintaining healthy gut microbiota, as it aids in the production of short-chain fatty acids, which are beneficial for gut health. Studies have shown that high-fibre diets foster a more diverse microbiota, often associated with better health outcomes.
On the other hand, high-fat diets are associated with a reduction in intestinal bacterial diversity. They can be particularly detrimental to infants, whose gut microbiome is still developing and more susceptible to imbalances. Excessive fat intake can be unhealthy, influencing the quantity and species of microbial metabolites, which in turn can impact human health.
The role of proteins is also noteworthy in diet. The type and quantity of protein intake can influence the production of microbial metabolites, which are crucial for gut health. Certain metabolites produced from protein fermentation have been linked with beneficial health effects, such as improved gut barrier function and anti-inflammatory properties. However, other metabolites can potentially have harmful effects if produced in excess, highlighting the importance of a balanced protein intake.
Dietary intervention is considered the most effective way to modify the gut microbiota and holds great potential in preventing and treating various health conditions. A balanced diet rich in diverse nutrients, including carbohydrates, proteins, and fiber, is essential for maintaining a healthy and diverse gut microbiota.
The role of medications, especially antibiotics, in influencing gut microbiota composition cannot be overstated. These therapeutic substances can often disrupt the delicate balance that exists within the gut microbiota, leading to decreased microbial diversity and in more severe cases, to a state known as dysbiosis. Dysbiosis refers to an imbalance or maladaptive change in the composition of the resident commensals, the community of microorganisms that live symbiotically in our bodies. These alterations in the gut microbiota can have serious implications for health and wellness, setting the stage for a variety of chronic diseases.
Over time, prolonged or recurrent use of certain medications can significantly reshape the gut microbiome, with potential long-term implications on health. For instance, it has been observed that chronic exposure to antibiotics can lead to persistent changes in the gut microbiota, favouring the proliferation of antibiotic-resistant strains. This disturbance in the microbial balance can also contribute to the development of complex health conditions such as obesity, inflammatory bowel disease, and even certain mental health disorders. Such findings underscore the importance of judicious medication use and the need for strategies that can help preserve or restore the balance of the gut microbiota following pharmacological interventions.
The composition of gut microbiota is susceptible to a myriad of lifestyle and environmental factors. It is well-documented that stress, inadequate sleep, and deficient physical activity can cause significant disruptions to the gut microbiota. For instance, the experience of chronic stress can lead to alterations in the gut microbiota structure, instigating an increase in potentially harmful bacteria. This shift can further exacerbate stress levels, creating a vicious cycle that negatively impacts overall health and wellness.
On the other hand, environmental factors also wield a substantial influence on gut microbial composition. Factors such as living conditions, exposure to infections, and pollutants can induce profound changes in the gut ecosystem. For instance, living in densely populated urban areas with high pollution levels can decrease microbial diversity. Similarly, exposure to certain infections can disrupt the delicate balance of gut microbiota, favouring the proliferation of certain microbial species over others. Therefore, maintaining a healthy lifestyle and a clean environment are crucial in preserving a balanced and diverse gut microbiota, which in turn supports overall health and wellness.
The composition of gut microbiota is influenced by a myriad of factors, among which genetics is significant. In fact, the relationship between our genetics and our gut microbiota composition is a dynamic and complex one. The MiBioGen consortium research provides valuable insights into this intricate relationship, highlighting the impact of host genetics on gut microbiota composition.
The research identifies certain genetic loci that affect the microbiome at a genome-wide significant threshold, highlighting the strong interconnection between our genes and the types of bacteria that populate our gut. For example, the lactase gene locus showed an age-dependent association with Bifidobacterium abundance, a type of bacteria that aids in the digestion of lactose. This finding demonstrates how our genetics can influence our gut microbiota, thereby impacting our ability to digest certain types of food.
Moreover, the research suggests that the gut microbiota might have causal effects in certain health conditions, such as ulcerative colitis and rheumatoid arthritis. This underlines the potential significance of our genetic predispositions on our gut health and, by extension, our overall health. The complex interplay between host genetics, gut microbiota composition, and human health is thus a crucial area of study, providing insights into our understanding of gut health and the development of potential therapeutic strategies.
The significance of diet in maintaining a healthy gut microbiota cannot be overstated. Dietary interventions, such as the inclusion of fibre-rich foods and the reduction of high-fat foods, have been shown to positively influence the gut microbiota, thereby enhancing physical function and potentially reducing mortality rates. Specific dietary changes can bring about significant shifts in the gut microbiota composition, illustrating the dynamism and responsiveness of this internal ecosystem to dietary inputs.
However, while the potential benefits of dietary intervention are substantial, it is essential to note that the field is still in its early stages of understanding. The relationship between diet, gut microbiota, and overall health is complex and influenced by many factors, including individual genetic makeup and lifestyle. Therefore, future research must continue exploring this area, focusing on individualised dietary interventions designed to optimise gut health and overall well-being. This underlines the necessity for personalised dietary interventions tailored to an individual's unique gut microbiota composition, moving towards a more personalised approach to nutrition and health.
We have navigated the intricate landscape of gut microbiota, uncovering how our dietary choices, health interventions, and daily habits shape it. In the next and final part of our series, we will investigate the ripple effects of exercise on gut microbiota, dissect the link between our eating habits and microbiota-related illnesses, explore the genetic factors at play, and discuss the therapeutic implications of our findings. Prepare for an insightful conclusion that will stitch together these threads, offering a blueprint for harnessing our gut microbiota in the pursuit of better health.
]]>
The urethra, in both men and women, is a critical part of the urogenital system. In men, it is the channel through which urine and semen exit the body. Historically, it was considered a rather simple biological tube, but recent discoveries have shed light on its complex interactions with microorganisms. These interactions are not just fleeting encounters; they can influence a man's health in profound ways.
In groundbreaking research led by Qunfeng Dong at Loyola University Chicago and David Nelson at Indiana University School of Medicine, scientists have made significant strides in understanding the microbial composition of the male urethra. Their findings, published in the reputable journal "Cell Reports Medicine," reveal that the urethral microbiome in healthy men is surprisingly simple yet profoundly important. This research utilized advanced scientific methods, such as shotgun metagenomics, to decode the genetic material of these microbes from urethral swabs of 110 adult males without signs of infection.
Imagine shotgun metagenomics like a sophisticated photographic technique that captures not just images but the very RNA of the bacteria found, providing unprecedented insights into their presence, type and abundance. It's a way to see the unseen, to understand the genetic stories of these microbes in exquisite detail.
The researchers found that Streptococcus, particularly Streptococcus mitis, holds sway in the male urethra, representing about a quarter of the bacterial population. Streptococcus mitis is a lactic acid-producing powerhouse, and this is crucial for a simple reason: lactic acid helps maintain the pH balance of the urethra, warding off hostile pathogens that could cause infections.
In essence, lactic acid is like the shield of the urethra, a chemical barrier that defends against microbial invaders. It is a testament to how our bodies are not merely passive vessels but active participants in maintaining health, leveraging the powers of friendly microbes to keep the bad ones at bay.
But the story doesn't end there. The researchers uncovered something intriguing: a secondary, more intricate microbiota in some men that resembles the bacterial populations found in the vagina. This includes Gardnerella vaginalis, notorious for its role in bacterial vaginosis in women—a condition where the protective Lactobacillus is overthrown by harmful anaerobic bacteria.
This complex microbiota was predominantly found in men who had engaged in unprotected vaginal intercourse, with these bacteria remaining detectable for up to two months afterward. This illuminates the dynamic and bidirectional nature of microbial exchange between sexual partners, where intimate contact becomes a conduit for bacterial colonization and recolonización.
The presence of these vagina-associated bacteria in the male urethra is a profound reminder that our bodies are not isolated islands but are profoundly affected by our intimate connections with others. It is a dance of microscopic entities across the landscapes of different bodies, influenced by the intimacy of human behavior.
The insights garnered from this study have vast implications. They provide a baseline of what a healthy male urethral microbiome should look like, serving as a reference point to identify deviations that could signal disease. The immune system's interaction with these microbes, particularly those transferred during sexual intercourse, becomes a crucial area for further investigation.
Understanding this could lead to innovative treatments or preventive strategies aimed at preserving the delicate balance of the urethral microbiota. For instance, could probiotics tailored to bolster beneficial bacteria in the urethra be a future therapeutic strategy? Could certain lifestyle changes or precautions during sexual activity influence the microbiome's health and stability?
Beyond individual health, the transfer and colonization of bacteria between partners also have implications for broader issues like reproductive health and pregnancy outcomes. Bacterial vaginosis, for example, has been linked to preterm delivery and low-birth-weight infants, highlighting the potential ripple effects of the microbial interplay within our bodies.
There are still many mysteries to unravel. How do these microbial shifts affect long-term health? Could they contribute to chronic urogenital conditions? How does the microbiome recover or stabilize over time after changes induced by sexual behavior? Research along these lines could pave the way for a more holistic understanding of sexual health, incorporating the concept of microbial balance in education and prevention strategies.
In the fight against sexually transmitted infections (STIs), which have a disproportionate impact on socioeconomically disadvantaged populations, this research offers a beacon of hope. It promises a new perspective on diagnosis and management, potentially transforming our approach to these pervasive health challenges.
In closing, the research by Dong and Nelson represents a leap forward in our understanding of the male urethral microbiome and its intricate ties to sexual behavior. As we continue to explore the fascinating world of the human microbiome, it is clear that our approach to health must respect the complex interplay of these microscopic communities with our behavior and overall wellbeing.
The more we learn about the microbiome, the more we realize that health is not merely the absence of disease but a harmonious balance of countless interactions within us. Embracing this complexity is key to unlocking new ways to promote health, prevent disease, and understand our own biology in the context of the living, breathing ecosystem that is the human body.
Sarah's world, once vibrant and full of color, had become a tapestry of grey, punctuated by recurrent episodes of intense pain. Each morning, she would wake up hopeful, yearning for a day free from the shadow of migraines. But the dark clouds of pain, unpredictably yet frequently, would roll in, distorting her perception and draining her vitality. For many, the term 'migraine' might evoke images of a severe headache, a temporary discomfort easily remedied with over-the-counter medication. But for Sarah, migraines were a tempest. They weren't just intense headaches; they were sensory tsunamis. They brought debilitating symptoms that were far more than just pain: distorted visions, like shimmering lights or blind spots, nausea that sometimes escalated to vomiting, and an extreme sensitivity to light and sound which forced her into isolation. Even the gentlest whisper or the dimmest light became unbearable.
The unpredictability of her migraines tormented Sarah. Activities like dinners or park outings could abruptly become painful ordeals. The world seemed full of unseen triggers, making every experience a potential risk. It was during a routine consultation that a doctor hinted at a possible link between her migraines and gut health, setting Sarah on a new path of discovery. But why did these migraines happen? And could there be a connection beyond the brain itself?
The intricate relationship between the gut and the brain is best exemplified by the vagus nerve, a vital connector stretching from the base of the brain to the abdomen. Acting as the primary communication channel, the vagus nerve reveals that our gut, often dubbed the "second brain" due to its extensive and dense Enteric Nervous System (ENS), isn't just a passive recipient of brain signals. In fact, a surprising 80% of the information flows from the gut to the brain.
This bidirectional communication means the gut can significantly influence our moods, behaviors, and health. For instance, gut distress can relay signals that manifest as anxiety or even exacerbate conditions like migraines. Conversely, stress from the brain can disturb gut functions.
Moreover, the Enteric Nervous System in our gut possesses more neurons than the spinal cord, allowing it to function and communicate even if the connection to the brain is severed. This independent operational capability showcases the gut's pivotal role in overall health. Many researchers now believe that nurturing a healthy gut environment can lead to improved brain function and reduced susceptibility to neurological issues, emphasizing the need to pay heed to our gastrointestinal well-being.
Every human has a unique gut microbiota, an ecosystem of bacteria, viruses, fungi, and more. This microbiota affects various functions, from digesting food to even influencing mood. When there's a dysbiosis – an imbalance in this ecosystem – the body might produce higher levels of pro-inflammatory cytokines.
Cytokines are protein molecules used in cell signaling. Some of them, like IL-1beta, IL-6, IL-8, and TNF-alpha, promote inflammation. In the context of migraines, levels of these cytokines rise during an attack. What's even more intriguing is that these same cytokines can stimulate nerves in the gut, leading to visceral pain, a distinct type of pain that feels like it's coming from your organs – often described as a deep squeeze or pressure.
When the gut is in a state of dysbiosis and inflammation, it can become more permeable – a condition colloquially known as 'leaky gut.' In this state, unwanted molecules can enter the bloodstream, leading to endotoxemia, a condition where harmful bacteria enter the bloodstream. One of the results? An overactive Hypothalamic-Pituitary-Adrenal (HPA) axis, which then produces excessive cortisol, our body's primary stress hormone. This chain of events can make individuals more prone to inflammatory conditions and, in the context of our discussion, possibly trigger migraines.
Expanding our understanding, it's essential to note that various neuroactive substances link migraines to the gut. Substances like CGRP, substance P, VIP, and neuropeptide Y play roles in both the brain and gut. For instance, the CGRP (calcitonin gene-related peptide) is central in migraine episodes. Intriguingly, it's also involved in regulating stomach acid and pancreatic enzyme production.
One more pathway worth mentioning is the tryptophan pathway. Tryptophan, an amino acid, can be metabolized into serotonin, a neurotransmitter that helps regulate mood, appetite, and sleep. Disruptions in this pathway have been noted in many gut-brain disorders, and it seems migraines are no exception.
The food we consume not only nourishes our bodies but also holds the power to shape the very environment of our gut. This, in turn, can have ripple effects on various health aspects, including the onset and severity of migraines.
Delving into the realm of specific digestive concerns, there's an intricate relationship between migraines and various digestive issues. Conditions like Helicobacter pylori infections not only present their set of gastrointestinal symptoms but can also indirectly influence the frequency and intensity of migraine episodes. This connection further emphasises the intertwined nature of gut health and neurological wellbeing.
Short-Chain Fatty Acids (SCFAs) and Migraines
Short-Chain Fatty Acids (SCFAs) play a pivotal role in gut health. These compounds are primarily produced when dietary fibers are fermented by the beneficial bacteria residing in our gut. Acetate, propionate, and butyrate are among the most significant SCFAs in this context. They work collectively to maintain the integrity of the gut barrier, modulate immune responses, and provide crucial energy to the cells of the colon.
Butyrate, in particular, deserves special attention. Beyond its role in the gut, butyrate has been described in the latest literature to play neuroprotective properties. It actively assists in preserving the integrity of the blood-brain barrier—a critical structure that regulates what substances from the bloodstream can access the brain. This function highlights the broader impact of gut-derived compounds on our overall neurological health.
Diamine Oxidase (DAO) and Migraines
Furthermore, the enzyme Diamine Oxidase (DAO) is essential in breaking down histamine in the body. A deficiency in DAO can result in excessive histamine levels which have been linked to migraines. Certain foods are high in histamine, including aged cheeses, smoked meats, and fermented foods. People with low DAO levels might find that consuming these foods exacerbates their migraines. As a result, many migraine sufferers are advised to follow a low histamine diet and may also benefit from DAO supplements.
Probiotic Supplementation and Migraines
Emerging research suggests that probiotic supplementation may have a modulating effect on migraine attacks. Though the exact mechanisms remain unclear, some proposed actions of probiotics in relation to migraines include promoting the production of Short-Chain Fatty Acids (SCFAs) in the gut, improving the epithelial integrity of the intestine, and suppressing the nuclear factor kappa-B (NF-κB) pathway. This suppression can lead to reduced levels of proinflammatory cytokines, which have been linked to migraine occurrences. Probiotics might also improve gastric emptying rates, alleviating a common gastrointestinal complaint among migraineurs: gastric stasis. This improvement is thought to occur via neuroimmune interactions. A randomized double-blind controlled trial even revealed the potential benefits of a 14-strain probiotic mixture for migraine patients.
Dietary Choices and Migraines
As usual, dietary choices can either promote or disturb the delicate balance of our gut microbiota. For instance, the consumption of certain foods might lead to an overgrowth of bacteria that produce Lipopolysaccharide (LPS). LPS is a known endotoxin, and when it finds its way into the bloodstream, it can trigger inflammatory responses. An elevated presence of LPS can be harmful to the brain and is speculated to be one of the factors exacerbating migraine attacks.
The Role of Dietary Fats
Dietary fats, especially omega-3 and omega-6 fatty acids, can influence inflammatory responses in the body. Omega-3 fatty acids, found in fish, walnuts, and flaxseeds, are known to have anti-inflammatory properties, which can be beneficial for migraine sufferers. On the other hand, excessive intake of omega-6 fatty acids, typically found in many processed foods, can promote inflammation. Maintaining a balance between these fats might aid in reducing migraine frequency and severity.
Vitamins and Their Impact on Migraines:
Certain vitamins have shown potential in migraine management:
Weight Management and Migraines
Obesity has been identified as a risk factor for the development of chronic migraines. Adipose tissue (fat cells) can produce inflammatory substances that might increase migraine risk. Hence, weight loss and maintaining a healthy weight can potentially reduce migraine frequency and severity. Adopting a balanced diet and regular physical activity can aid in weight management and, in turn, migraine management.
Incorporating a holistic understanding of posbiotics, probiotics, fats, vitamins, and weight management can provide migraine sufferers with more tools and strategies in their battle against this debilitating condition. As with all dietary and lifestyle changes, it's essential to consult with a healthcare professional before making significant alterations.
In essence, a deeper understanding of diet's role in the gut-brain axis can offer insights and potential strategies for those grappling with migraines, underlining the profound connection between what we consume and our neurological health.
The journey from the complexity of the gut-brain connection to understanding its implications for conditions like migraines is intricate but illuminating. As we unpack the layers of this relationship, from microbiota to cytokines, from SCFAs to neuroactive substances, we find a dance of intricate pathways and interactions. For Sarah, and many like her, this expanding knowledge offers hope. The promise is clear: By understanding and nurturing our gut, we might just hold the key to managing and potentially alleviating debilitating conditions like migraines.
]]>
As research continues to uncover the complexities of the human microbiome, there is growing evidence of a strong connection between gut microbes and mental health. This connection is called the Gut-Brain Axis. This topic has been a subject of interest for many years, with various studies exploring the links between the gut-brain axis and conditions such as depression and anxiety.
A recent study published in Nature Microbiology examines the relationship between gut microbial metabolism and mental health. The study, conducted by researchers at KU Leuven in Belgium, surveyed a large cohort of individuals and examined the correlation between microbiome features and quality of life indicators.
The human gut is home to many microorganisms, including bacteria, viruses, and fungi. These microorganisms comprise the gut microbiome, which plays a crucial role in many aspects of human health, from digestion and nutrient absorption to immune function and hormone regulation.
Recent research has also linked the gut microbiome to mental health, with evidence suggesting that disruptions to the microbiome could contribute to developing conditions such as anxiety and depression. This link is thought to be due to the complex interactions between the gut and the brain, which are mediated by the microbiome and the nervous system.
The researchers behind the Catholic University of Leuven conducted a large-scale metagenomics study to explore the links between gut microbes and mental health. The study involved surveying a cohort of over 1,000 individuals and examining the correlation between microbiome features and quality-of-life indicators, including depression.
The results of the study were striking. The researchers found that individuals with a higher quality of life indicators tended to have higher levels of butyrate-producing Faecalibacterium and Coprococcus bacteria in their gut microbiome. Additionally, Dialister and Coprococcus spp. were found to be depleted in individuals with depression, even after controlling for the effects of antidepressant medication.
One of the study's most interesting findings was identifying the neuroactive potential of gut microbes. Using a module-based analytical framework, the researchers assembled a catalogue of the potential neuroactive properties of the gut microbiome.
The analysis revealed that the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid was positively correlated with mental quality of life indicators. Additionally, the research indicated a potential role for microbial gamma-aminobutyric acid (GABA) production in depression.
The results of this study have important implications for our understanding of the links between gut microbes and mental health. Identifying specific gut microbes associated with higher quality-of-life indicators could pave the way for targeted interventions to improve mental health outcomes.
Additionally, the discovery of the neuroactive potential of gut microbes opens up new avenues for research into the mechanisms underlying the gut-brain axis. By understanding how gut microbes influence brain function and behaviour, researchers may be able to develop new treatments dubbed psychobiotics for a range of mental health conditions.
The latest research provides compelling evidence of the important link between gut microbes and mental health. The findings of the Flemish Gut Flora Project study highlight the potential of the microbiome as a target for interventions aimed at improving mental health outcomes. As research in this field continues, we may better understand the complex interactions between the gut and the brain, opening up new possibilities for preventing and addressing mental health conditions.
In recent times, SIBO (Small Intestinal Bacterial Overgrowth) has found its way from medical journals to trending social media topics. With its symptoms echoing those of the more common IBS (Irritable Bowel Syndrome), the condition has garnered attention from not just the medical community but also from a broader audience. Interestingly, social media influencers, even those without backgrounds in health or fitness, have been vocal about their experiences, leading to a wave of self-diagnoses predominantly among young adults, teens, and particularly among young females and girls. This article delves into the intricate relationship between SIBO and IBS, the advancements in diagnostic techniques, and the increasing importance of understanding the role of the gut microbiome in overall health.
Irritable bowel syndrome (IBS) is a functional bowel disorder produced by recurrent abdominal pain at least once a week in the last three months. It is associated with changes in stool form or stool frequency [1]. Symptoms must arise at least six months before diagnosis. Bloating, constipation, diarrhoea, incontinence, and psychological disturbances are some of the various comorbidities experienced by these patients.
IBS has been associated with stress and anxiety. The brain-gut axis is fundamental in understanding IBS [2]. As a result, many treatments were focus on antidepressants and neurobehavioral intervention [3]. Apart from these different pathophysiological mechanisms had been proposed to explain de IBS symptoms as visceral hyperalgesia, intestinal permeability, immune activation, altered gastrointestinal motility, autoimmunity, and alteration of the gut microbiome [1].
The gut microbiome has received significant interest over the last years. Abundant literature has shown a direct relationship between IBS symptoms and disorders of the gut microbiota. One manifestation of this dysbiosis associated with IBS is the small intestinal bacterial overgrowth [SIBO].
The Gold standard for diagnosing SIBO is the presence of ≥ 103 colony-forming units per millilitre (CFU/mL) of jejunal aspirate by culture [4, 5]. However, aspiration is invasive and expensive and requires a skilled gastroenterologist.
The breath test is a simplified way to measure SIBO. This study is based on the measurement of gases produced by bacterial fermentation and exhaled on the breath. Hydrogen (H2) and methane (CH4) are an example of them [6-8]. To stimulate bacterial fermentation, we use different types of carbohydrates such as glucose and lactulose. Glucose is a monosaccharide easily absorbed in the proximal small intestine. In contrast, lactulose is a disaccharide that has limited absorbability since it is not digested by host enzymes. [9]. The SIBO symptoms including bloating, abdominal pain, nausea, constipation, and diarrhea, are very similar to the IBS ones.
A positive H2 breath test is diagnostic of SIBO, which has been associated with diarrhea predominant IBS (IBS-D) and IBS with mixed bowel habits (IBS-M) [10]. A positive CH4 breath test shows methanogen overgrowth, associated with constipation-predominant IBS (IBS-C) [5, 11, 12].
The relationship between SIBO and IBS was described in a meta-analysis. 25 case-control studies were included, involving 3.192 IBS subjects and 3.320 controls. The prevalence of SIBO in IBS was 31.0% (95% CI 29.4–32.6) with an OR of 3.7 (95% CI 2.3–6.0, p = 0.001) compared to controls [13].
Previous studies have shown that infectious gastroenteritis [14, 15] are associated with the development of IBS, which have been termed post-infectious IBS (PI-IBS). This is another evidence of the relationship between IBS and the gut microbiota.
Infectious diarrhoea is known to cause intestinal permeability [16,17], and a similar phenomenon is seen in patients with IBS, especially in patients with stress [18]. This is thought to be partially mediated through bacterial effects on tight junctions [19]. The mechanisms how intestinal permeability persists after the acute infection, can be explained by the dysbiosis of the gut microbiome.
A decline in the gut's microbial biodiversity can set off a chain reaction of health issues. Without a balanced representation of bacterial species, certain strains might proliferate unchecked, potentially leading to disorders like SIBO. It's like removing a predator from an ecosystem and seeing an explosion in the population of its prey, which can have cascading effects on the environment.
One pivotal study, as reported by the Javier Santos Group in Barcelona, illuminated this connection. Their findings showed a discernible decrease in butyrate-producing bacterial families in subjects diagnosed with IBS-D [20]. When the populations of these butyrate-producing bacteria dwindle, the gut may become more susceptible to inflammation, increased permeability, and the consequent manifestation of IBS symptoms. This critical insight underscores the importance of maintaining a rich and varied gut microbiome to preempt or mitigate digestive disorders.
Different treatments for SIBO and IBS are target in the microbiome. The use of a non-absorbable oral antibiotic, rifaximin, is the one with the highest level of success. A meta-analysis that evaluated normalization of a breath test in response to antibiotics for SIBO found that rifaximin was the most common used. A metanalysis by Shah et al. found that antibiotics relieve symptoms in 81.6% of patients. Only five studies reported eradication of SIBO, and 93% of patients with a glucose breath test achieved normalization, while 71.4% of patients diagnosed via small bowel aspirate culture reached normalization [13]. Furthermore, treatment with specific antibiotics results in decreased CH4 levels correlated with constipation improvements [21,22]. Of note, while neomycin and rifaximin can each reduce constipation in IBS-C, using a combination of both appears to be most effective [23].
Probiotics have also been evaluated in the treatment of IBS. A systemic review by Ford et al. [24] found that certain combinations of probiotics may help IBS. However, there was significant heterogeneity between the studies. Interpretation of probiotic studies' metanalyses is difficult since different strains are studied in different combinations assessing various endpoints. Many studies also have small sample sizes, making it hard to generalize the results.
The exhaled gas hydrogen sulfide [H2S] could be another potential marker of bacterial overgrowth. H2S appears to be implicated in multiple gastrointestinal disorders with pro- and anti-inflammatory properties [25]. Singer-Englar et al. described an association between diarrhea and exhaled H2S levels [26]. This could be a factor implicated in patients with IBS-D.
In today's age of digital information, SIBO has found a spotlight on social media, particularly with influencers sharing their personal narratives. However, it's imperative to tread with caution. The intricacies between SIBO and IBS aren't straightforward, and the symptoms of both can easily be conflated. It's vital not to confuse dysbiosis with a mere growth in the number of CFUs. The presence or abundance of specific microbial strains or taxa does not directly equate to the manifestation of symptoms.
Furthermore, while breath tests are gaining traction as a diagnostic tool, their relationship with the overall bacterial abundance, as measured by 16S rRNA sequencing, remains to be definitively established. Self-diagnosis, especially based on popular narratives, can lead to misinterpretations. Always seek expert medical advice before drawing conclusions about one's gut health. It's essential to separate trending online topics from genuine medical conditions, ensuring that our understanding is rooted in science and expert guidance.;
Because of its therapeutic potential, more research on IBS and SIBO is necessary.
A new study prospective study published this week in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, explored the associations between vitamin D supplementation and incident of dementia.
According to Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”
The study was conducted by the National Alzheimer's Coordinating Center and included 12,388 participants who were dementia-free at baseline. The participants were categorized based on their exposure to vitamin D: D+ for those who had been exposed to vitamin D prior to dementia onset and D- for those who had not. The study included various formulations of vitamin D, and the researchers explored potential interactions between exposure and model covariates.
The study found that vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure. Participants who had been exposed to vitamin D supplementation had a 40% lower incidence rate of dementia compared to those who had not been exposed.
In fact, 75% of people in the study who didn’t take vitamin D developed dementia within 10 years. Of those who took vitamin D, 25% also developed dementia.
The researchers found that vitamin D gave greater protective benefits among women than men, although protection among both sexes was significant compared to not taking any vitamin D. Also, protection appeared to be better if people started taking the supplement before any signs of cognitive issues.
According to the study, vitamin D exhibited more protective effects among women than men. However, both sexes experienced significant protection compared to non-users. Moreover, the study suggests that starting the supplementation before the onset of cognitive issues may yield better results.
According to the study, individuals who carried the APOEe4 gene, associated with a higher risk of Alzheimer's dementia, had significantly less protective effects from vitamin D than non-carriers. The authors proposed that carriers of the APOEe4 gene may have better clearance of vitamin D from their intestines, potentially reducing the effectiveness of vitamin D supplementation. However, the hypothesis was not tested through blood level measurements.
Previous research has indicated that low vitamin D levels are associated with a higher risk of dementia, and vitamin D can aid in clearing amyloid in the brain, a hallmark of Alzheimer's disease. Furthermore, studies suggest that vitamin D may also offer protection against the buildup of tau, another protein involved in the development of dementia.
Figure 1 - (A) KM curve of dementia-free survival over 10 years, stratified by exposure to vitamin D. (B) Adjusted HR for dementia across vitamin D exposure groups.
Vitamin D is an essential nutrient that plays a vital role in bone health and immune system function. It is known that vitamin D deficiency is widespread, especially in the elderly population. Additionally, vitamin D deficiency has been associated with various health conditions, such as cardiovascular disease, diabetes, and cancer.
The study's findings support the idea that vitamin D may be a crucial factor in preventing dementia. However, the study was observational and not a randomized controlled trial(RCT). This means that it's possible that other factors could have affected the results; for example, people who choose to take vitamin D supplements may have other lifestyle choices that contribute to their health outcomes.The researchers did not intervene in the participants' vitamin D intake.
Therefore, the study cannot establish causation between vitamin D supplementation and dementia prevention. Nonetheless, the results of the study provide valuable insights into the potential benefits of vitamin D supplementation.
It is worth noting that the study did not specify the optimal dose of vitamin D required for dementia prevention. The recommended daily intake of vitamin D varies across different age groups and health conditions. The best way to determine the appropriate dose of vitamin D is to consult a healthcare provider.
Dementia is a global health challenge that requires urgent attention. While there is no cure for dementia, research has suggested that certain lifestyle factors, such as maintaining a healthy diet and exercise regimen, may reduce the risk of developing the disease. The study discussed in this article suggests that vitamin D supplementation may also play a significant role in preventing dementia. Further research is needed to establish causality and also determine the optimal dose of vitamin D required if causality is finally established.
Consuming oats comes with a load of benefits.
Oatmeal is an energy-dense cereal with a low glycaemic index, which means that it is slowly absorbed and has no sugar spike. It’s suitable for everyone but is best for the active and sporty type that seeks to maintain energy levels throughout the day.
Oats have a perfect mix of soluble and insoluble butyrate-producing fibre, helping maintain top intestinal flora and daily regularity. Oats are recognised to improve the ratio of good to bad cholesterol, reducing the risk of cardiovascular diseases.
Oats are relatively high in protein, with almost 13 grams per 100 g; Oats usually come fortified with iron and Vitamin B12, helping with red blood formation and preventing anaemia.
Oats can help you maintain a healthy balance of good bacteria in the gut. However, if your microbiota is off-balance, consuming high amounts of oats can backfire, as your microbiota will likely produce too much gas, leading to bloating and indigestion. If this is your case, start with small amounts and slowly increase intake as your body adapts.
Check out our three super easy-to-make and nutritious recipes to control your heart and tummy.
Ingredients to make the base dough:
Toppings to add that extra flavour: * Mix one or two – don’t overdo it!
Directions:
Ingredients:
Directions: Combine rolled oats, blueberries, Greek yoghurt, soy milk, cinnamon, and sugar in a lidded jar. Makes sure the oats have enough milk to soften. Cover, shake to mix and refrigerate for 10 hours to overnight.
Quick and easy breakfast, packed with deliciousness to prepare in under 10 minutes.
Ingredients:
Directions:
1.- Melt the butter in a saucepan. Add brown sugar and the apples. Cook for 5 minutes and occasionally stir over medium heat.
2.- Stir in apple cider, milk, cinnamon, oats, and salt. Cook for 3-5 minutes, frequently stirring, until oatmeal is creamy and thickened and apples get a little crunch (too much time and cook to mush).
We trust you liked our recipes. Don’t forget to comment and let us know how your gut did with these treats!
Nothing complements fibre-rich food better than supplemental butyrate. So, don’t forget to head to our store and order your bottle now!
]]>According to Nassos Typas [1], Group Leader and Senior Scientist at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, “Only now people are recognising that drugs and our microbiome impact each other..." Typas said that these interactions might have a critical consequence on our health.
Peer Bork, Director of Scientific Activities at EMBL, added, “This calls for us to start treating the microbiome as one of our organs.”
But acknowledging this fact is just the first step toward predicting individual health outcomes when administering a drug to a patient based on the host’s microbiome.
The final goal would be to predict an individual’s response to various commonly used pharmaceuticals based on their microbiome to maximise the chances of experiencing the desired positive health outcome aimed in the first place.
Researchers realise that varying individual reactions to medications seen in their clinical practice may well be modulated and tied to an individual’s gut bacteria. Medical health professionals must consider whether the patient’s expected therapeutical response and side effects might be influenced by their microbiota. Health professionals also need to consider how prolonged treatments might entice strain-specific microbiota changes that would, in turn, reduce the drug's effectiveness or its dosage.
The optimal goal would be to predict patient responses depending on their microbiome composition, allowing health care providers to individualise drug treatments and modulate them in time as the treatment progresses. Navigating this intricate and complex issue may seem daunting to health professionals and patients, as the complete knowledge of microbiome-to-drug interactions still eludes us due to its mounting complexity.
Several research groups are systematically trying to map drug and bacteria interactions, describe how microbes transform them and, eventually, try to predict the effect this biotransformation might entice. A newly published study by Nature revealed 70 bacteria-drug interactions [2] after investigating the depletion of 15 structurally diverse medications by 25 representative gut bacteria strains. Nearly half of these bacteria-drug interactions were previously unknown and never reported before this study.
There is still a lot that we do not understand about the microbiome. Further research is necessary to realise the mechanism governing these processes.
The final goal would be to predict an individual’s response to various commonly used pharmaceuticals based on their microbiome to maximise the chances of experiencing the desired positive health outcome aimed in the first place. Here is what we have learned so far:
Microbiota treats oral drugs as just another chemical and transforms them in the gut most often than not. This adds a new layer of complexity to a drug’s pharmacokinetics (the process by which a drug is absorbed, distributed, metabolised and eliminated by the body). This microbiota-mediated chemical transformation of drugs to secondary metabolites can alter the therapeutic response in patients.
More often than expected, researchers realised that the microbiome acted on the drug like a bomb diffuser: the microbiome can reduce the potency or concentration of a drug to render it partially ineffective. In some cases, researchers reported this unwanted effect and instances of drugs becoming toxic after microbiota alterations. This biotransformation [3] could partially explain the ample range of reported side effects described for any given drug on the market. This fact is strain-dependent: distinct bacterial species within the microbiome transform certain medications while others do not.
Medications affected by the phenomena range from OTC medications to life-saving drugs, including antivirals and chemotherapeutic agents. Scientists primarily employ microbiome-depleted or germ-free animal models to identify these microbiotas-drug interactions. To test for bacterial specificity, they pain-snakingly administer specific bacterial isolates to germ-free animals along the drug to be tested and record the observable interactions.
Although this one-by-one approach is perfectly valid, it does not allow for the generalisation of humans that host a complete microbiome. The complex strain-to-strain interactions with a drug may result in outcomes different from those reported in the individual models.
Besides biotransformation, it is now known that common pharmaceutical drugs eventually accumulate in the microbiome, altering their bacterial function, which, in turn, may change how the drug is transformed in the first place.
Drug bioaccumulation not only transforms the metabolism of the bacteria but also acts as a drug reservoir, which may lead to toxicity concerns. Researchers continue to discover what medications bond to metabolic enzymes in the gut bacteria, altering the from that very same bacterium.
Original studies have focused primarily on the pharmacokinetic effects of life-saving therapeutics, including:
Accepting that the patient’s microbiome is an obligatory gatekeeper to any given drug treatment may help us formulate new ways to use this fact to our advantage. If our microbiome represents a critical health and disease modifier, modulating it before any drug treatment to align with its purpose might positively increase its positive effects on the underlying condition.
Thus, the microbiome becomes a clinically significant pharmaceutical target [4] in itself. In long-term drug treatments for chronic illness, the individualised approach would be somewhat like this:
This new approach might suit long-term treatments, such as psychiatric disorders. In these cases, powerful medications are taken chronically, with often variable and declining results, as the treatment sometimes spans an entire life span [5].
A recent 2020 GUT publication assessed drug-microbe associations [6] for specific drugs. That was the case for the following list of drugs:
Several studies point out how SCFAs produced by specific microbiota may contribute to metformin's therapeutic effect on glucose homeostasis, improving the body’s ability to control insulin resistance.
However, scientists feel the need to explore the effect of polypharmacy – the use of five or more medications by an individual taken daily. Since nearly one-fourth (24%) of patients [8] in England take three or more prescription drugs (and half of those patients take five or more), scientists felt it was necessary to examine polypharmacy's impact on gut microbiota. This compound effect generates more outstanding orders of complexity in the microbiota-drug interactions.
As research groups focus on the microbiome-to-drug interactions, one must consider the possible roles the gut-derived metabolites produced by the same bacteria under study may have on these drugs. These effects may range from chemical to drug reactions and bindings, resulting in deactivation or activation to possible alterations of active transport of the drug through the mucosa. Bacterially derived metabolites might act as agonists or antagonists to the drug within specific cell receptors, enhancing or reducing the drug's effect within the target cells.
One such described case may be metformin [9], a blood glucose-lowering oral drug with intriguing new applications in ageing [10], gut homeostasis [11] and even as a chemotherapy adjuvant [12].
Favourable, functional gut microbiota is usually linked to short-chain fatty acid (SCFA) [13] producing bacteria. SCFAs include acetate (C2), propionate (C3) and butyrate (C4). These SCFAs accumulate many science-described roles in gut normal functions, including nutrient digestion, absorption and bowel movements. On top of all the processes in which they are involved, they also seem to play further roles in the metabolisation and effect of certain drugs.
For example, several studies point out how SCFAs produced by specific microbiota may contribute to metformin's therapeutic effect on glucose homeostasis [14], improving the body’s ability to control insulin resistance [15]. Furthermore, compared to others, some patients' gut microbiome SCFA-producing profile offered relief from the adverse gastrointestinal effects of metformin.
The gut microbiome in humans is an intricate ecosystem. The exchange between commonly used non-antibiotic drugs and gut microbes is equally complex and bidirectional.
Drugs can influence microbiome composition and vice versa. The gut microbiome can also affect a person’s response to a medication. It does this by enzymatically changing the drug’s structure and modifying its bioactivity, bioavailability or toxicity.
Gut microbiota also indirectly impacts a person’s reaction to other non-pharmaceutical treatments, like supplements and dietary wellness products. However, further studies are needed to determine how these treatments affect gut health.
In the study conducted by EMBL and funded by the European Commission Horizon 2020 [16], researchers caution that the study’s findings impact only the bacteria grown in the lab. More research is required to comprehend how gut bacteria medication bioaccumulation manifests inside the human body.
Vitamin D has been making headlines as the pandemic evolved for the past two years, as researchers linked it to competent immunity. While vaccination seems crucial in reducing the risk of acute life-threatening COVID-19, it does not guarantee complete immunity against the virus. As a precautionary measure, and even if fully vaccinated, the public has been encouraged to strengthen their immune system. [3]
In a time of social responsibility, one may ask, “what can I do to enhance my immune system to reduce the severity of a more than possible COVID-19 infection? “
To that effect, a new and insightful systematic review from Borsche, Glauner and Mendel, 2021 [4] three independent novel authors that despite no previous publications, may have written a relevant paper that could help clarify this question and spark a productive conversation.
The novel German researchers set to demonstrate the hypothesis that Vitamin D3 deficiency, is one of the main reasons for severe SARS-CoV-2 infections and that supplementation might be the easiest and simplest action one may take to improve the odds. In the researchers own words: “Could a virus that is spreading so easily and is much deadlier than H1N1 influenza be kept under control if the human immune system could work at its fullest capacity?”
After a thorough triage of the available clinical and epidemiological papers published in the past 18 months for COVID and Vitamin D, the researchers identified 8 out of 44 published studies for quality and statistical potency. The studies included several meta-analyses, hospital studies for 1,607 patients and one general population study that spanned 19 countries.
"Could a virus that is spreading so easily and is much deadlier than H1N1 influenza be kept under control if the human immune system could work at its fullest capacity?” Borsche et al. 2021
The resulting statistical analysis showed a strong correlation between serum Vitamin D levels as a marker of a patient's immune competence and resilience against respiratory tract infections, including SARS-CoV-2. The resulting correlations based on the available papers show that the higher the serum Vitamin D3, the more likely to experience a mild to asymptomatic COVID-19 infection. So much so, that theoretically and per extrapolation, COVID mortality would approach zero as blood serum Vitamin D3 hit 50 ng/mL [4].
The authors conclude that "... strong evidence that low D3 is a predictor rather than just a side effect of the infection." and that “[the authors] strongly recommend combining vaccination with routine strengthening of the immune system of the whole population by vitamin D3 supplementation to consistently guarantee blood levels above 50 ng/mL (125 nmol/L)”.
To understand how Vitamin D may work against the virus, it is essential to remember what COVID-19 does to the body. The most life-threatening event in the course of a COVID-19 infection is the Acute Respiratory Distress Syndrome (ARDS) mediated by multiple mechanisms, including an out of control, dangerous immune response to the infection called "cytokine storm". ARDS results in fluid accumulating in the lungs' air sacs, leading to a significant decrease in oxygen reaching the bloodstream and difficulty breathing. [5]
A cytokine storm occurs when immune cells rapidly and uncoordinatedly release a flood of cytokines into the bloodstream to fight the viral infection, causing more harm than good, including multiple organ dysfunctions. [6]
According to the authors, SARS-CoV-2 virus interferes with the normal regulation of the body’s system to control blood pressure and volume. This system is called the renin-angiotensin system (RAS). The virus prevents a key component of the system called Angiotensin II to convert to Angiotensin-(1,7) by inhibiting the enzyme responsible for this step. The virus hijacks this enzyme called ACE2 to enter cells, leaving Angiotensin II to accumulate. This accumulation then triggers vasoconstriction and results in inflammation, fibrosis, and oxidative stress that eventually leads to ARDS. [4,7] Vitamin D counteracts this virus hijack, by stimulating the ACE2 enzyme to clear Angiotensin II to Angiotensin-(1,7) which tapers down the route to ARDS .
Prior research has also shown that Vitamin D3 can potentially attenuate the inflammatory response due to viral infection by increasing regulatory T Cells (Treg) - immune cells that curb excessive immune response to maintain homeostasis. Tregs would prevent the unleash of cytokine storm, while conserving the ability of the immune system to coordinate its response to the viral infection. [8]
Considering these new independent findings, it would seem logical to advise the public to increase its Vitamin D levels to better react to a COVID-19 infection, escape any future variants, or offset decreasing antibody activity.
However, current Vitamin D recommendations seem far too low to attain the desired pre-emptive protection level and improve the odds of future infection outcomes.
Historically, serum Vitamin D recommendations were initially established over a century ago at 20 ng/ml to prevent rickets, the softening, and the weakening of children's bones. [9] Current WHO recommendations upped the level and set it at 30 ng/ml in the late 20th century.
One repeated primary concern preventing higher levels of Vitamin D recommendations relies upon the widespread belief that higher supplementation would increase the risk of calcium deposits in the arterial lining. However, it is now known that adequate levels of Vitamin K2 prevent arterial calcification as Vitamin K2 directs available calcium to the bones rather than the vascular walls. [10]
"To maintain these blood levels [40-60 ng/ml] with minimal sunlight exposure, a person would require ingestion of 4000–6000 IUs of vitamin D daily" Charoenngam et al. 2021
More voices in the scientific and medical community are pushing the current WHO recommendation of serum Vitamin D3 levels from the low 30's to over 50 ng/ml. Last year, a review on "Immunologic Effects of Vitamin D on Human Health and Disease" suggested serum Vitamin D3 levels between 40 to 60 ng/ml. [11] According to the study: "To maintain these blood levels with minimal sunlight exposure, a person would require ingestion of 4000–6000 IUs of vitamin D daily." Charoenngam et al. 2020.
Borsche et al. also conclude in their review that Vitamin D supplementation ranging from 4000-10000 IU /day to generate the desired new levels of 50 ng/ml is safe if levels of Vitamin K2 are at 200 µg/ml. [4] It is also important to note that Vitamin K2 may interfere with some anticoagulant medications, so if it is advisable to consult with a health professional for individualised advice.
Multiple publications support the correlation of Vitamin D3 to benefits other than Musco-skeletal maintenance, including proper immune function.
As the pandemic evolved during the past two years, accumulating and statistically significant epidemiological data seem to confirm that pre-infection Vitamin D3 status may be a factor correlated with COVID-19 infection positive outcomes.
Although further research is needed to enlighten further the mechanisms by which Vitamin D3 protects during a COVID-19 infection, more voices in the scientific community have started to propose the regular supplementation of this common Vitamin as a preventive agent for current and future immune challenges, including those of the respiratory tract.
Disclaimer:
This Article is for educational purposes only and must not replace advice from your own health care provider. Always consult your own doctor before taking any medication or supplements.
The hallmarks of atherosclerosis are:
Atherosclerosis is associated with the metabolic syndrome disorders: Type 2 diabetes; obesity; and hypertension. Inflammatory response to an initial dysfunctional condition is common to all of them. Also common to all of them is an interplay with the gut microbiota, where the initial signs of the disorder modify the gut microbiota composition which then further develops the disorder. (The link between the gut microbiota and type 2 diabetes was discussed in a recent blog article).
As is the case for metabolic syndrome disorders, the development of atherosclerotic plaques is associated with changes in gut microbiota composition [2]. In atherosclerotic subjects, there is a relative abundance of bacteria associated with inflammation, such as Enterobacteriaceae and Streptococcus, and a depletion of short chain fatty acid (SCFA) producing bacteria, such as Roseburia intestinalis. Amongst their other biological roles, SCFA’s, especially butyrate, help maintain the gut wall lining responsible for selective transfer of substances from the gut to the blood stream. In addition, the bacterium Akkermansia muciniphila, which is intimately associated with the epithelial cells and tight junctions between them in the gut wall lining, is also depleted in atherosclerosis.
Inflammation is central to the process of atherosclerotic plaque formation. Chronic excess cholesterol initiates an inflammatory response that starts the process of plaque formation. However, similar to what happens in Type 2 diabetes, the changes in gut microbiota composition that accompany the development of atherosclerosis (as described in the previous paragraph) boost the level of inflammation by causing the gut wall barrier to leak, allowing lipopolysaccharides (LPS’s) to pass into the blood. LPS molecules, which shed from the cell walls of certain bacteria in the gut, are potent initiators of inflammation.
In 2011, Stanley Hazen’s laboratory at the Cleveland Clinic developed an interesting hypothesis connecting a specific gut microbiota metabolite with atherosclerosis [1,4]. According to this hypothesis, choline from eggs and carnitine from meat, can be converted by some bacteria in the gut to the metabolite trimethylamine (TMA) which is subsequently taken up into the blood stream and transported to the liver where it is oxidized to trimethylamine oxide (TMAO). The hypothesis links TMAO to increased formation of atherosclerotic plaques though the mechanism is not known [1]. If this hypothesis proves correct, it would provide a direct link between eggs and meat and atherosclerosis, carrying with it the suggestion of treatment by dietary restriction (not the first time that there has been a call for restricting eggs and meat to people with heart disease). The hypothesis has been received with enthusiasm by many in the field but there are critics who point out that fish, considered beneficial for atherosclerosis, contains high endogenous levels of TMAO. There is also evidence that carnitine is beneficial for atherosclerosis [3]. Furthermore, choline is an essential nutrient which should not be overly restricted. So clearly, this matter requires further study.
Inflammation is central to atherosclerosis as well as to the metabolic syndrome disorders. The gut microbiota is not responsible for the initial inflammatory steps. Rather, it plays a secondary, though no less important, role in this process, transforming acute inflammation into chronic inflammation. This means that readjustment of the microbiota has the potential to wind back these disorders, once we have a more complete understanding of the processes involved.
Vitamin D and maintaining immune defenses are also correlated [3]. Current research found that over 80% of 200 COVID-19 patients in Spain had Vitamin D deficiency [4]. Further limited studies and meta-analyses have observed that Vitamin D seems to reduce symptoms of COVID-19 as compared to standard care [5]. However, more substantial data is needed to support its impact in decreasing mortality rates of hospitalized patients.
We now know that there is evidence to back up the benefits of Vitamin D in the body. Still, the research community debates its ability to prevent diseases. In particular, one study concluded that Vitamin D supplementation did not improve the bone strength of old adults in the US [6]. Another clinical trial concluded that Vitamin D supplementation did not prevent cancer and cardiovascular disease in aging adults [7].
These mixed findings on the benefits of Vitamin D have been a mystery to scientists, until now. Researchers at the University of California (UC) San Diego recently revealed a possible explanation for this discrepancy and a new understanding of Vitamin D bioavailability [8].
Like any other substance, Vitamin D comes in several forms. Typically, researchers determine Vitamin D levels in the body by conducting standard blood tests, which only detect an inactive form of Vitamin D stored in the body called 25 hydroxyvitamin D or 25(OH)D.
The body benefits from Vitamin D only when the inactive precursor metabolizes into its active form - 1,25 dihydroxyvitamin D or 1,25(OH)D. So no matter the amount of sun exposure or supplementation you take in, you only gain the benefits once activation of Vitamin D occurs in the body.
UC San Diego researchers have suggested that the Vitamin D paradox, where studies failed to establish a correlation in Vitamin D supplementation, blood inactive Vitamin D status, and positive health outcomes, might be due to scientists measuring in the blood 25(OH)D, the inactive form of Vitamin D, rather than its active form 1-25(OH)D.
In addition, UC San Diego researchers found a consistent association between 1-25(OH)D levels, the active form of Vitamin D, and the diversity and number of bacteria in the gut microbiome. In contrast, 25(OH)D, the precursor form of the vitamin, had a weak correlation with the “friendly” gut bacteria. The link between active Vitamin D levels and gut microbiome trumps other factors investigated in the study, such as antibiotic use, ethnic background, and even location.
The study also pointed out that participants with the highest levels of active Vitamin D have the most gut bacteria that produce butyrate. This short-chain fatty acid results from bacteria feeding on fibre and has been known to have potential benefits to support the gut lining, maintain the gut microbiome, and further support a competent immune system [9].
Researchers believe that butyrate-producing gut bacteria, rather than high quantities of inactive Vitamin D, control Vitamin D activation, which could explain these seemingly contradicting findings
Contrary to prior logic, participants living in sunnier places did not have significantly higher levels of active Vitamin D as other participants, despite synthesizing high amounts of inactive Vitamin D through the skin. Researchers believe that butyrate-producing gut bacteria, rather than high quantities of inactive Vitamin D, control Vitamin D activation, which could explain these seemingly contradicting findings.
Moreover, there is increasing evidence that the microbiome and immune system are interconnected and that active Vitamin D and butyrate may play extensive roles in this dynamic [10].
All of this points to butyrate helping our body transform the inactive precursor to the active form of Vitamin D, allowing us to reap all the benefits for optimal well-being.
Vitamin D supplementation and sunlight appear to be insufficient for optimal Vitamin D bioavailability and turnover. We need to encourage our bodies through gut microbial diversity, including butyrate-producing bacteria, to directly influence Vitamin D metabolism to its active form. Consequently, supplementing Vitamin D with butyrate ensures that we get all the benefits of Vitamin D to promote a sound mind and body while maintaining a favourable gut microbiome to support our immunity and overall well-being.
The hallmarks of Type 2 diabetes are: 1. an excess of dietary glucose; 2. reduced insulin production; and 3. decreased sensitivity to insulin (called insulin resistance). The gut microbiota affects all these elements.
The gut microbiota makes additional glucose and other sugars available to its host by degrading complex carbohydrates present in the gut which the host’s digestive system could not. Mice raised germ-free (a condition that can only be maintained in a laboratory), and, thus lacking gut microbiota, typically have less body fat than those raised conventionally. But when these germ-free mice are seeded with gut microbiota from conventionally raised mice, they soon develop as much fat as the conventional mice. The source of this fat is the additional sugars and metabolites made available by the microbiota. In addition, the microbiota upregulates the host’s metabolic storage pathway, storing the energy from these nutrients in fat storage cells, though how it does this is not known.
Sensitivity to insulin decreases with chronic high blood glucose well before one becomes diabetic. There are also noticeable changes in gut microbiota composition, one being a decrease in butyrate producing bacteria.
The chronically high blood glucose levels characteristic of obesity and prediabetes initiate inflammation in the pancreatic islets where insulin is produced. If the inflammation becomes chronic, islet cells will die, thus reducing insulin output. Deleterious changes in the gut microbiota contribute to this chronic state of inflammation. The same chronically high blood glucose levels that initiate inflammation in the pancreatic islets also affect the composition of the gut microbiota. Under such conditions, the population of microorganisms that produce short chain fatty acids (SCFAs) decreases significantly. One of the roles of SCFA’s is to maintain the integrity of the gut wall lining, the semipermeable membrane that selectively controls what enters the host’s blood stream. As SCFA levels decrease, the gut wall becomes more permeable, allowing lipopolysaccharides (LPS’s) to pass into the blood. LPS’s are toxic molecules that shed from the cell walls of certain bacteria (whose numbers also increase with chronically high blood glucose). LPS’s are potent initiators of inflammation, so as they continuously feed into the blood, the inflammation becomes chronic.
Sensitivity to insulin decreases with chronic high blood glucose well before one becomes diabetic. There are also noticeable changes in gut microbiota composition, one being a decrease in butyrate producing bacteria. When gut microbiota is transplanted from lean healthy human males into males who are prediabetic the transplant recipients become more sensitive to insulin and the composition of their gut microbiota changes, becoming similar to that of the donor. Studies in mice have linked such increased insulin sensitivity to an increase in butyrate producing bacteria in the gut. Unfortunately, the improved insulin sensitivity and the changes in microbiota composition only last for several months, indicating that host and diet exert an ongoing influence on microbiota composition.
The composition of the gut microbiota influences the essential elements of Type 2 diabetes by determining what undigested materials will be degraded, what products will be produced, and in what quantities. While much research has been done in the last 20 years, much more needs to be done to understand the mechanisms and other details that will allow us safely to provide effective solutions for prevention and treatment of Type 2 diabetes.
Our gut not only contains our microbiota, but it also hosts up to 600 million neurons. These nervous system starts developing after conception, even before the first neuron in our foetal brain. Popular wisdom has always recognized that the gut is our “second brain”, but it seems that it may well be our first brain.
Our brain is continually receiving and processing information from the exterior as well as the interior. It is now believed that up to 60-80% of the internal information received by the brain comes from the gut. This strong bidirectional connection between the gut and the brain is called the “Gut-Brain Axis” or (GBA).
One of the key players in this bi-directional link is, of course, our gut microbiota.
Your microbiota uses this vital link to make itself be noticed. It sends chemical signals up to your brain through this Axis. It is now believed that those sugar cravings at night might not be you brain spoiling your diet, but a temper tantrum from specific bacteria in your gut that are not getting the food they were used to receive. Once you eat the candy, the microbiota releases sugars and certain fatty acids that give you this temporary “high”. The jury is still out if microbiota is responsible for the “follow up regret” or is just your mind being hard on itself.
Your microbiota may affect your mood, as well. It seems that your microbiota would be running the show and affecting your behavior. This potential influence of your microbiota may have in your brain is the most provocative.
But this gut-brain connection not only stops there. Growing evidence shows that altered gut-brain communication seems to be correlated with some of the most predominant psychological disorders that plague western societies.
The list of conditions under research is growing, and an altered microbiota is often cited as a critical factor in severe conditions. These conditions range from depression linked to Irritable Bowel Syndrome (IBS), migraines, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, to neuropsychiatry disorders as depression, anxiety, schizophrenia and even autism. Most of these disorders are characterized by distorted gut-brain communication that is influenced by external stimuli [1, 2].
Everyday stresses can disrupt the microbiota in your gut, and thus, can impact the Gut-Brain-Axis [3, 4]. These stressors can include:
Our gut microbiota feeds from the food we eat and produces by-product chemicals, just like a car running on fuel that sheds emissions.
However, beneficial bacteria produce by-products that are utilized by the gut and even can travel to distant organs like the brain. They act as small essential messengers relaying chemical information throughout your body. Some of these chemicals are now termed by scientists as "postbiotics".
Some of such postbiotics are Short-Chain Fatty acids (SCFA), gamma-aminobutyric acid (GABA) or serotonin (the happy hormone). For example, a study showed that meals high in legumes that rise the production of acetate in the hindgut could have a distant effect and curb appetite in the brain [5].
Not all these messengers are derived from microbiota but may be activated or controlled by the microbiome. For example, Vitamin D has also been showing to influence the immune system due to its strong connection with the microbiota, suggesting it could be employed in combination with pre and probiotics to improve the immune response [6, 7].
Originally, back in 2013, psychobiotics were defined as “a live organism that, when ingested in adequate amounts, produced a health benefit in patients suffering from psychiatric illness. As a probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act in the gut-brain-axis”[8].
After 2017, the term psychobiotic was broadened to include prebiotics or the fibre that acts as food for the psychobiotic. In fact, is the combination of the prebiotic, the probiotic and the resulting postbiotics what would comprise as a more realistic definition of a psychobiotic. These metabolites include butyrate, serotonin, gamma-aminobutyric acid to name a few.
Although the idea of using probiotics to improve psychological well-being through the brain-gut axis first appeared as far as 1880 and were popularized with 1907 Metchnikoff's works on yoghurt and longevity [11], it was not until the last decade that this idea was tested in preclinical studies with varying degree of success. The outcome of these trials was highly dependent of each product tested and the complexity of the condition under observation.
Psychobiotics are exciting news; Not all pre, pro or postbiotics may be classified as psychobiotics. For example, TMA derived from dietary choline is a compound believed to be a marker of cardiovascular risk. This would be an example of a postbiotic that is not linked to better outcomes, and couldn't be classified as a psychobiotic as it seems to have negative effects in our well-being.
We are still a long way from figuring out what exactly drives our mental well being and how we can intervene effectively. So far, we know that a happy, stable gut may contribute to bring peace to our brain [9, 10]. We are still very far from deciphering the complex and intricate relationship between the gut and the brain. However, psychobiotics may be well prove to be a first baby step towards this ambitious goal.
Since the 1940s, antibiotics have significantly reduced illness and death from microbial infections. However, rampant and indiscriminate use of these drugs pushes microbes to develop defence strategies to adapt and survive in their presence by altering specific genes. As the microbes defeat the drugs meant to kill them antimicrobial resistance (AMR) develops. These antibiotic-resistant germs can quickly spread through our ecosystem (water, soil, food), further allowing their resistance genes to be transferred to other naïve microbes. Thus, AMR has developed into a substantial global health threat, and various approaches, involving alternatives to antibiotics, are being proposed to mitigate this threat.
A healthy and balanced gut microbiome can play a critical protective role in the fight against AMR. Scientists are proposing the use of helpful gut microbes or probiotics instead of antibiotics to treat infections. The hypothesis is that this approach can alleviate the pressure to survive, which leads to the development of AMR in disease-causing microbes. Instead of killing harmful bacteria using antibiotics, establishing and strengthening the good gut bacteria can hinder the growth of disease-causing microbes which are competing for the same space. In fact, the restoration of healthy gut microbiota can not only reduce the number of harmful microbes in the gut but also provide additional benefits, such as the production of antimicrobial compounds and boosting the body’s immune response which can improve overall resistance to infections. The use of probiotics is also becoming more popular in livestock agriculture where it is substituting antibiotics used for growth promotion of animals. However, it is essential to remember that probiotic microbes are not exempt from the natural processes that govern the development of AMR, and careful screening for resistance genes before application of probiotics to fighting AMR is crucial to the success of this approach.
Most probiotics are readily susceptible to changes in temperature, pH etc. This poses significant hurdles in maintaining the stability of probiotic products and ensuring the delivery of sufficient live (viable) probiotics to humans and animals. Thus, the focus is gradually shifting to achieving similar benefits using ‘non-viable’ products derived from bacteria– the so called postbiotics. They represent all the molecules secreted by live bacteria into the culture medium they grow in or those that are released after the bacterial cell breaks open. Postbiotics include enzymes, secreted proteins, short-chain fatty acids, vitamins, amino acids, antimicrobial peptides, and organic acids.
Instead of killing harmful bacteria using antibiotics, establishing and strengthening the good gut bacteria can hinder the growth of disease-causing microbes which are competing for the same space
Antimicrobial and anti-adhesion proteins secreted by the probiotic bacteria can target gut pathogens by either directly killing them or preventing them from attaching to our gut. The anti-adhesion property can be particularly useful in preventing biofilm formation by pathogens making the infection more accessible to traditional antibiotics. This can reduce the dose of antibiotics required and potentially prevent the development of AMR. Postbiotics can help overcome some of the limitations of live gut microbes, such as the presence of AMR genes and opportunistic infections. They also offer the advantage of being more stable and can be purified explicitly in large amounts and used for targeted delivery to combat diseases.
Bacteria naturally present in foods, or those deliberately added to them, including probiotic bacteria, represent a massive reservoir of antibiotic resistance genes. The ingestion of such foods can influence the abundance and diversity of resistance genes we carry, contributing to the spread of AMR. On the other hand, a suitable dietary intervention can positively impact the prevalence of antibiotic-resistant microbes in our gut. Some studies have shown that the inclusion of non-digestible carbohydrates can significantly reduce the numbers and variety of antibiotic-resistant bacteria in the gut.
Thus, the food and added probiotics we eat, our natural gut microbiome, and the antibiotics we consume, dynamically intersect with each other and play an essential role in shaping the antibiotic resistance gene pool we harbour. Gut microbes, postbiotics and diet, therefore, represent interesting points of intervention and manipulation in our fight against AMR.
Editors Note: This experiment conducted by Harvard Medical School demonstrates how bacteria rapidly accumulate successful mutations in a short time. New strains develop as they encounter increasing exponential concentrations of an antibiotic.
In a ‘stable’ state, gut cells link together and form a strong barrier against harmful microbes and molecules. As with the skin, the gut is also supplied with a variety of immune cells ready to clear any harmful microbes that break through the barrier. But this barrier must allow nutrients in, so the gut barrier loosens or tightens to regulate the flow of substances to the tissue and blood vessels on the inside of the body [2]. Once substances enter the blood, they can reach and affect distant sites in the body, such as the skin. A range of substances influences the skin, including products released from the microbiota and immune and gut cells [3].
The gut may play a part in keeping the skin healthy through many different processes. For example, the gut microbiota can contribute to wound healing by helping gut cells absorb molecules that aid skin repair, or by directly releasing these types of products themselves [4]. The gut microbiota can also restore skin to a healthy state after damage, re-establishing appropriate immune response levels in the skin after UV exposure [5]. Animal studies have shown that supplementing the gut microflora can also improve skin thickness, flexibility and hydration [1].
Once substances enter the blood, they can reach and affect distant sites in the body, such as the skin. A range of substances influences the skin, including products released from the microbiota and immune and gut cells.
The diversity of the gut microflora, the relative proportions of different species, and/or their contact with the immune system may influence inflammatory skin conditions, such as psoriasis and eczema. Changes in the gut microflora can generate products that activate immune cells, which could cause inflammation in the skin [3]. The gut microflora also generates products that are anti-inflammatory and strengthens the gut barrier, such as short-chain fatty acids [6]. Short-chain fatty acids were found to be relatively low in some eczema cases [7], suggesting further investigation is needed into the role of the microbiota and these substances in eczema.
Complex gut–brain interactions may play a role in inflammatory skin conditions, such as acne. Under psychological stress, such as anxiety and depression, chemicals that activate neurons can be released from the gut. These chemicals loosen the gut barrier and move through the barrier into the blood, where they move around the body and can cause inflammation in the skin [1] — highlighting the complex interplay between the gut and distant regions of the body.
The gut may influence the skin in a variety of ways from helping repair wounds to stimulating inflammatory responses. With complex systems involved full impacts on skin are still be revealed. Surprisingly, a more in-depth look at our gut may shed light on ways to look after our skin.
Research has revealed the importance of the GM in human health. It has also shown how changes in the population of the GM microorganisms may lead to disease. This phenomenon is called 'dysbiosis'. Our life choices such as dietary habits, smoking, exercise, antibiotic overuse may affect the GM composition and lead to dysbiosis. Conditions that may be associated with dysbiosis range from heart diseases, GIT disorders, cognitive issues, and even cancer. The 'healthy' GM is stable throughout adulthood, but with ageing, there is a decline in this stability. A series of factors may impact the composition and diversity of the GM explained below.[2]
During ageing, the functionality of our body declines- organs and cells throughout the body and in the GIT age. The immune system is not so efficient in responding to challenges. Notably, there is low-grade systemic inflammation observed in older people called 'inflammageing', which is associated with age-related conditions.
Older populations show altered patterns of food consumption and altered motility in their GIT. Usually, the ability to chew and to swallow deteriorate with age. We still lack conclusive data from human studies that demonstrate what if any hormonal and enzyme alterations in older age lead to these changes.[3]
Other factors that impact the GM composition are changes in the socioeconomic status of older people that lead to lifestyle changes (e.g. less physical activity) and poor diet (e.g. less variety in food). Also, increased poly-medication, recurrent antibiotic use and increased incidents of admission to long-term care units are a challenge for the 'healthy' GM.
Older populations show a higher prevalence of diabetes, cardiological issues, cognitive decline, 'sarcopenia' and 'frailty. Such conditions are often associated with GM alterations. Sarcopenia refers to significant muscle loss and weakness. Sarcopenia leads to a general state of diminished functionality and increased dependability. The two syndromes are gaining medical interest because of their potential severe outcomes in the elderly.[4]
The 'aged' GM is often characterised by a low diversity of species and the loss or low proportions of certain beneficial microorganisms that are more abundant in younger adults. In a simple scheme, there are beneficial GM bacteria that thrive with a healthy diet and are responsible for breaking down complex sugars and carbohydrates from food. This activity results in the production of SCFA, such as butyrate. According to the latest Science, it may be involved in anti-inflammatory responses. This decline in beneficial bacteria gives a chance to potentially harmful species to increase. An alarming example of this is the increased incidents of the life-threatening infection with Clostridium difficile among hospitalised older people.[5]
As we age our microbiota's diversity is reduced, further accelerating the progressive decline associated with age. Maintaining your microbiota diversity can help you curb biological ageing.
But it is not all gloomy for the ageing population. Based on science, we can improve the dysbiosis that comes with ageing and therefore manage healthier ageing. Diet plays a crucial role in the maintenance of a 'resilient' and 'healthy' GM throughout our lives and during ageing. A plant-based diet with a plethora of vegetables and fruits can maintain and improve diversity in the GM by nourishing the beneficial microorganisms in our gut. Potentially the following can play a role in ageing management:
Vitamin D helps us absorb calcium, keeping our bones and teeth healthy. We get vitamin D from our diet or generate it in our skin (converting an early form of cholesterol into vitamin D). Enzymes must first activate vitamin D before it can act in the body. Activated vitamin D sticks to a protein known as the ‘vitamin D receptor’ or VDR, switching on an array of genes [1]. Vitamin D receptors are found in cells all over the body, suggesting vitamin D may have many more roles than maintaining bones. With these receptors found in types of gut and immune cells, we explore how vitamin D may influence gut immunity.
The intestine is tasked with allowing the right substances (such as nutrients) to pass through into the body while restricting access to harmful substances. A single layer of cells in the intestine stands between the body’s external (lumen) and internal environments — protecting the body from unwanted guests, such as harmful microbes (or ‘pathogens’) [2].These gut cells may sound slight, but they are sandwiched between two further layers. Below the gut cells sits tissue that houses a range of immune cells, and on top of the gut cells is a sticky mucus that faces out to the lumen. Resting on top of this mucus layer is our gut microbiota: the non-harmful community of microbes that call the gut their home [3]. With the vast number of microbes that live in and pass through the gut, immune cells, gut cells and the microbiota can work together to offer a barrier against invading pathogens [4].
Vitamin D not only helps regulate our mineral turnover for bones and teeth, but also has a relevant role in immunity and cell replication
As mentioned above, the gut forms a barrier to the outside environment, stopping pathogens passing through to the internal environment of the body and causing disease. To form a strong barrier, cells in the intestine stick together through various molecules, including a set of proteins called ‘tight-junction’ proteins. Vitamin D may strengthen this barrier by increasing the number of tight junction proteins between the cells [5]. Vitamin D may also help these cells to neutralize pathogens. Short sections of proteins known as ‘antimicrobial peptides’ damage microbial cells or recruit immune cells to remove microbes [6]. Both immune and gut cells can release forms of these antimicrobial peptides. And, through the vitamin D receptor, activated vitamin D can switch on genes inside immune and gut cells to generate antimicrobial peptides [1].
In addition to protecting the gut against pathogens, Vitamin D may also keep immune cells in check. Vast numbers of microbes live in the gut, many of them beneficial. If the immune system is over activated, it can cause autoimmune or inflammatory diseases. Vitamin D can dampen immune responses by causing immune cells to release proteins that suppress the immune system and reduce inflammation [7]. Scientists are assessing Vitamin D in relation to inflammatory diseases in the gut. Still, the full role of Vitamin D may be more complex [5].
Vitamin D may have many roles in gut immunity, such as strengthening the gut barrier and triggering cells to release antimicrobial peptides. Vitamin D may also mediate immune responses in the gut and research is ongoing to elucidate its impacts on inflammatory diseases.
As microbiota grows and differentiates in a baby’s gut, it actively engages with a repertoire of immune cells. Through constant interaction with the microbiota these cells learn these basic simple rules:
The immune cells achieve these objectives, effectively sensing and sampling not only the gut microbiota but also some small molecular motifs that the microbiota constantly sheds as debris called microbe-associated molecular patterns or MAMPS. Immune cells start to differentiate between the familiar patterns that normal residents shed and those from aliens or pathogens. The immune system learns to intervene only when the situation changes and new unknown and possible harmful bacteria is sensed.
The young gut immune system is like fuzzy teenage recruits in boot camp, trained by the microbiota. These newbie trainees “learn” to cooperate and respond to different “threats”. They are divided into sub-groups which specialize in various tasks. Each group uses alien weaponry; some carry “rifles”, other “machines guns” and others man the “artillery”. They learn to work together and call upon other groups as need be.
Similarly, the gut microbiota actively trains the immune soldiers (cells) to mount a defence against “threats” and learn when to “sound-off “ the alarm when just friendly bacteria are going about their day. The microbes achieve these tasks either by interacting directly with immune soldiers or indirectly by releasing substances which activate immune cells that only tackle the pathogens.
For instance, the microbiota influences and coordinates the production of antibodies by special immune cells located in the gut. This antibody is an immune-protective molecule known as immunoglobulin Ig(A). Ig(A) is secreted in linked pairs in the gut where microbes reside. These antibodies specifically attach and neutralize pathogens, and the toxins these pathogens are constantly shedding that irritates the gut lining[1]
The friendly beneficial or commensal microbiota assist the host in preventing pathogen infection stimulating the production of anti-microbial factors, gaining space and resources to thrive. Thus, intestinal microbiota contributes to the establish a long-term balance of gut immunity: resisting pathogenic infections, whereas not mounting a response to friendly bacteria. While all of this is occurring in the gut, the protection is systemic. That is, immune cells that are “primed” (trained) in the gut, will eventually migrate to sites as distant as the brain where they form a new immune colony, ready to counteract any local threat.
Intestinal microbiota contributes to the establish a long-term balance of gut immunity: resisting pathogenic infections, whereas not mounting a response to friendly bacteria
Several types of experiments have been designed to learn how gut microbiota helps mature our early immune system. Experiments with germ-free (GF) animals (animals bred in sterile, microbe-free environment) or experiments that manipulated the microbiota (either by antibiotic treatment or microbial reconstitution), showed that an altered gut microbiota results in an impaired or inadequately developed immune system.
Researchers noticed two critical aspects of this immune chaos
In fact, the absence of a friendly microbiota, or an altered microbiota is like having no teacher at all or a bad teacher that sends mixed signals to the immune system. If there’s no microbiota, the immune system is never exposed to any bacteria to learn from. Why train or create strong communication links if there’s no one at the gates? GF Mice, for example, show a “leaky” unstructured gut wall, with loosely linked cells at the border. It makes sense, why bother maintaining a wall if there is no need to defend it?
On the other hand, a disruptive, unhealthy microbiota is like having a mean teacher that instead of teaching the kids, stirs unrest, provokes chaos and joins the party-throwing chairs out the window. This sustained situation sends contradictory signals to the immune cells that enter an internalized state of hyperactivity, in which they fail to differentiate between friendly bacteria, rogue pathogens and normal gut functioning; the situation becomes so chaotic that even immune cells end up turning against normal cells. This abnormal microbiome to immune cells relationship is correlated with a higher occurrence of autoimmune diseases (AID). Such IAD can be local as inflammatory bowel disease, or even systemic like rheumatoid arthritis, multiple sclerosis, and type 1 diabetes.
While perinatal and early postnatal events are critical periods for the establishment of gut microbiota, as individuals, we may have little control over them. However, as with genes, one may feel that the microbiota developed during our early years is final. If gene therapy seem to finally be able to edit our genes effectively, we certainly can also take positive actions during adult life to help reconstitute the balance in our gut. Diet, intermitted fasting, exercise, along with the use of pre-, pro- and post-biotics may help your immune system to rekindle with a more beneficial microbiota resulting from a more positive environment.