Butyrate enemas upregulate Muc genes expression but decrease adherent mucus thickness in mice colon

Abstract

Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an endproduct of carbohydrate fermentation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not.

Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress‐induced depressive‐like behavior

“…SCFAs promote intestinal barrier maintenance and stimulate epithelial regeneration, leading to mucus production and a trophic action on the mucous membrane (Lewis et al, 2010). Butyrate affects goblet cell‐specific MUC2 expression and thereby alters epithelial protection (Gaudier et al, 2009). Given that the intestinal mucous layer is an important component of the intestinal barrier, the relative number of goblet cells and the content of glycoproteins were further analyzed.…”

Dietary supplementation of Viligen™ to Nile tilapia improves growth and gut morphology

“…In this study, fish fed diets supplemented with VILIGEN™ had higher goblet cell numbers in the proximal intestine than those in the control group. Mucus provides chemical protection against toxins and antigens and has bactericidal properties that reduce the bacterial population in direct contact with the epithelial surface (Corfield et al, 2000; Gaudier et al, 2009; Hoebler et al, 2006). Thus, one could speculate that the gut mucosa of fish that received diets containing VILIGEN ™ had greater protection against infections.…”

Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor

“…butyrate with or without 10 mM MCPA or 1.5 mM of the PHD2 inhibitor IOX2 acutely for 1 h. Daily 100 mM butyrate enemas over weeks have been used therapeutically in both rat and mice animal studies and human clinical trials. [32][33][34] Doses for MCPA and IOX2 were selected to be optimized for their influences as well as be tolerated in the rapid 1 h time point, which was selected as Olenchock et al 17 demonstrated that 2-OG levels increased in liver tissues after pharmacological PHD inhibition to a peak within 10 minutes and decreased to nonsignificant levels after 4 h. Furthermore, in addition to the possibility that butyrate could inhibit PHDs and elicit measurable responses in a rapid manner, we targeted 1 h to decrease the likelihood of seeing metabolic shifts due to butyrate metabolism in addition to PHD inhibition alone, similar to our T84 in vitro studies.…”