Abstract
Inflammatory bowel disease (IBD) is associated with a loss of intestinal barrier function and dysregulated immune responses. It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs. In this study, we investigated the effects of SCFAs in comparison to highly specific GPR43 agonists on human intestinal epithelial and immune cells. Our results confirm that SCFAs are enhancers of barrier function in intestinal epithelial cells. Additionally, SCFAs also displayed potent immunoregulatory properties based upon the ability to inhibit LPS-induced cytokine production in PBMC, and human T cell proliferation and cytokine production. Unexpectedly, and in contrast to the current belief, specific GPR43 agonists failed to exhibit similar barrier enhancing and anti-inflammatory properties. These findings demonstrate that SCFA possess broad protective functions in IBD and agonizing GPR43 alone is unlikely to be beneficial in patients.
Highlights
The human intestine harbors hundreds of trillions of bacteria that belong to thousands of different species
Our results reveal that short chain fatty acids (SCFAs) were potent enhancers of intestinal barrier function and inhibitors of immune cell activation; but GPR43 agonists were incapable of substituting for SCFA
The demonstration that the protective effects of SCFA in inflammatory bowel disease (IBD) models were abrogated in the absence of GPR43 provided strong evidence that GPR43 mediated the protective effects of SCFA during intestinal inflammation in these specific models [25, 34, 35]
Summary
The human intestine harbors hundreds of trillions of bacteria that belong to thousands of different species. The microbiota share a symbiotic relationship with their host by aiding in carbohydrate digestion, vitamin synthesis, xenobiotic metabolism, strengthening of the intestinal barrier, providing protection from pathogenic infections, and the development of an appropriately regulated mucosal immune system. Unhealthy changes in the microbial community (dysbiosis) are capable of resulting in diseases such as inflammatory bowel disease (IBD). IBD is a condition wherein genetic and environmental factors converge to culminate in dysregulated immune responses in the gastrointestinal tract.
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