Antibiotic resistance and postbiotics

Antibiotic resistance is inherent to microbes' nature

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 Balanced Gut Microbiota could reduce the need to use antibiotics

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.

Postbiotics a novel approach to assisting microbiota to AMR resistant pathogenic infections

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.

 

Double-Edged Sword Effect of exogenous bacteria

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.

Conclusions

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.

[1] Imperial, I. C., & Ibana, J. A. (2016). Addressing the Antibiotic Resistance Problem with Probiotics: Reducing the Risk of Its Double-Edged Sword Effect. Frontiers in microbiology, 7, 1983.

[2] Nataraj, B.H., Ali, S.A., Behare, P.V. et al. Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods. Microb Cell Fact 19, 168 (2020).

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