Vitamin D and gut immunity: more than bones

What is Vitamin D?

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.

What do we mean by ‘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

Vitamin D and our gut immunity

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].

What’s next?

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.

[1] Nurminen, V., Seuter, S., & Carlberg, C. (2019). Primary Vitamin D target genes of human monocytes. Frontiers in Physiology, 10.

[2] MacDonald, T. T., & Monteleone, G. (2005). Immunity, inflammation, and allergy in the gut. Science, 307(5717).

[3] Assimakopoulos, S. F., Triantos, C., Maroulis, I., & Gogos, C. (2018). The Role of the Gut Barrier Function in Health and Disease. Gastroenterology Research, 11(4).

[4] Chassaing, B., Kumar, M., Baker, M. T., Singh, V., & Vijay-Kumar, M. (2014). Mammalian gut immunity. Biomedical Journal, 37(5).

[5] Yamamoto, E. A., & Jørgensen, T. N. (2020). Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity. Frontiers in Immunology, 10.

[6] Auvynet, C., & Rosenstein, Y. (2009). Multifunctional host defense peptides: Antimicrobial peptides, the small yet big players in innate and adaptive immunity. FEBS Journal, 276(22).

[7] Charoenngam, N., & Holick, M. F. (2020). Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients, 12(7).

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