Eat your fiber. We have all heard it before. You may be thinking, “My digestive system is fine! I don’t need fiber.” But, whether you like it or not, fiber has countless health benefits outside of normalizing bowel movements such as maintaining a healthy weight, lowering cholesterol levels, and as current research suggests: aiding your immune system. Research conducted by scientists at Purdue University identifies how short chain fatty acids (SCFAs), which are produced from the fermentation of dietary fiber, are important for mediating host immunity through the enhancement of antibody responses.  

Research conducted by Myunghoo Kim and colleagues observes the impact of dietary fiber and SCFAs on the production of the antibody IgA and antibody secreting cells known as B cells.  Our respiratory and gastrointestinal tracts are vulnerable to microorganisms, and IgA is an antibody that plays an important role in lining these mucosal surfaces in attempt to prevent infection. As a first line of defense of the immune system, IgA prevents attacks of pathogenic organisms by blocking access to epithelial receptors and trapping them in the mucosal linings.  In order to assess the impact of different levels of SCFAs on these antibodies, Kim and colleagues fed mice with special diets containing high, medium, and low levels of dietary fiber. They found that the quantity of B cells decreased in mice that were fed low levels of dietary fiber and increased in mice that were fed high levels of dietary fiber, suggesting that high dietary fiber (DF) boosts host immunity. Furthermore, mice were treated with a dose of antibiotics that suppressed gut microbiota and therefore SCFA production. This gut microbiota suppression prevented DF from increasing IgA activity in the mesenteric lymph nodes, Peyer’s Patches (lymphoid in the small intestine), spleen, blood serum, and in the colon. These results confirm that the gut microbiota is in fact responsible for the systemic antibody response.

After establishing that SCFAs do in fact aid the immune system, Kim and colleagues revealed multiple mechanisms by which this occurs.  One such mechanism is the regulation of genes required for B cell differentiation (B cell maturation into antibody-secreting plasma cells) via histone deacetylase inhibition (HDACi).  The enzyme HDACi can affect transcription by inducing acetylation of histones, and regulating transcription factors and other proteins that contribute to DNA transcription. In the process of histone acetylation, acetyl groups are added to N-terminus of histone proteins. In turn, this removes the positive charge of these proteins and thus reduces the affinity between the histones and the DNA. The goal of this process is to allow transcription factors to bind more easily to DNA sites and enhance gene expression. One example of this mechanism found by Kim and colleagues is that SCFAs act to turn on the gene Aicda, which promotes antibody diversification and B cell activation.

Further study revealed that SCFAs can also directly induce the differentiation of naive B cells into those that express immunoglobulin G (IgG). One of the many functions of IgG includes binding to pathogen surfaces, which are then recognized and digested by phagocytic immune cells. It also aids in the formation of a cascade known as a complement system, which allows for stimulation of these phagocytic cells to kill pathogens. Thus, SCFAs help convert human B cells into antibody-secreting plasma cells through gene expression or direct inducement, promoting the elimination of pathogens from the body.

Lastly, SCFAs were also shown to mediate host immunity through their role in metabolism.  SCFAs are converted to acetyl CoA which is integrated into the Krebs Cycle to generate ATP. This increases cellular metabolism, which helps offset the costly process of antibody production and B cell differentiation. Acetyl CoA is also an important player in fatty acid synthesis, especially the synthesis of palmitic acid, which aids in B cell antibody production. Myunghoo and colleagues observed that there were increased numbers of cellular lipid droplets of palmitic acid present in B cells to provide a reservoir of lipids for production of IgG. Furthermore, glycolytic activity (the rate at which glucose is broken down to extract energy for cellular metabolism) increased in B cells due to SCFAs. This faster metabolism provides the available energy necessary for antibody synthesis. Overall, SCFAs allow for increased ATP production and fatty acid synthesis so the taxing process of B cell antibody production can occur.

As current research indicates, the role of dietary fiber is not simply confined to our digestive system, but our body at large, including the immune system. Since fiber intake for an average adult in the United States is only about half of the daily recommended amount of 25-38 g/day, increased consumption of foods high in dietary fiber should become a critical public health goal. In addition, research pertaining to dietary fiber holds promise in the prevention and treatment of diseases. Several studies are being conducted on colon cancer and its relation to SCFA production, including one which suggests that the effects of SCFAs on human colon cancer are associated with histone acetylation. This may open the door for designing foods that regulate histone acetylation and thus gene expression within specific locations of the body in order to inhibit inflammation and tumor growth of cancer cells.


REFERENCES

Bouma, H. (2010, August 27). AMP-activated protein kinase as a target for preconditioning in transplantation medicine. PubMed. Retrieved October 3, 2016, from NCBI.

Myunghoo, K. (2016, August 10). Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host and Microbe. Retrieved October 3, 2016.

Xu, W., Parmigiani, R., & Marks, P. (n.d.). Histone deacetylase inhibitors: Molecular mechanisms of action. Retrieved October 03, 2016, from Nature.com.

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