The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

Does an Apple a Day Also Keep the Microbes Away? The Interplay Between Diet, Microbiota, and Host Defense Peptides at the Intestinal Mucosal Barrier.

A crucial mechanism of intestinal defense includes the production and secretion of host defense peptides (HDPs). HDPs control pathogens and commensals at the intestinal interface by direct killing, by sequestering vital ions, or by causing bacterial cells to aggregate in the mucus layer. Accordingly, the combined activity of various HDPs neutralizes gut bacteria before reaching the mucosa and thus helps to maintain the homeostatic balance between the host and its microbes at the mucosal barrier. Defects in the mucosal barrier have been associated with various diseases that are on the rise in the Western world. These include metabolic diseases, such as obesity and type 2 diabetes, and inflammatory intestinal disorders, including ulcerative colitis and Crohn's disease, the two major entities of inflammatory bowel disease. While the etiology of these diseases is multifactorial, highly processed Western-style diet (WSD) that is rich in carbohydrates and fat and low in dietary fiber content, is considered to be a contributing lifestyle factor. As such, WSD does not only profoundly affect the resident microbes in the intestine, but can also directly alter HDP function, thereby potentially contributing to intestinal mucosal barrier dysfunction. In this review we aim to decipher the complex interaction between diet, microbiota, and HDPs. We discuss how HDP expression can be modulated by specific microbes and their metabolites as well as by dietary factors, including fibers, lipids, polyphenols and vitamins. We identify several dietary compounds that lead to reduced HDP function, but also factors that stimulate HDP production in the intestine. Furthermore, we argue that the effect of HDPs against commensal bacteria has been understudied when compared to pathogens, and that local environmental conditions also need to be considered. In addition, we discuss the known molecular mechanisms behind HDP modulation. We believe that a better understanding of the diet-microbiota-HDP interdependence will provide insights into factors underlying modern diseases and will help to identify potential dietary interventions or probiotic supplementation that can promote HDP-mediated intestinal barrier function in the Western gut.

Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration.

Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.