Oral tributyrin treatment affects short-chain fatty acid transport, mucosal health, and microbiome in a mouse model of inflammatory diarrhea

Abstract

Butyrate may decrease intestinal inflammation and diarrhea. This study investigates the impact of oral application of sodium butyrate (NaB) and tributyrin (TB) on colonic butyrate concentration, SCFA transporter expression, colonic absorptive function, barrier properties, inflammation, and microbial composition in the colon of slc26a3^-/- mice, a mouse model for inflammatory diarrhea. In vivo fluid absorption and bicarbonate secretory rates were evaluated in the cecum and mid-colon of slc26a3^+/+ and slc26a3^-/- mice before and during luminal perfusion of NaB-containing saline and were significantly stimulated in both slc26a3^+/+ and slc26a3^-/- colon by NaB. Age-matched slc26a3^+/+ and slc26a3^-/- mice were either fed chow containing 5% NaB or gavaged twice daily with TB for 21 d. Food and water intake, weight, and stool water content were assessed daily. Stool and tissues were collected for further analysis of SCFA production, barrier integrity, mucosal inflammation, and microbiome analysis by 16S rRNA gene sequencing. 5% NaB diet did not exert a significant impact on SCFA levels, mucus barrier, or inflammatory markers, but significantly increased oral water intake. TB gavage treatment increased the expression of SCFA transporters Mct1 and Smct1, mucus content and microbial diversity, and decreased the neutrophil marker Lipocalin 2, Phospholipase A2, and the antimicrobial peptide Reg3b in the slc26a3^-/- cecum. However, TB treatment also resulted in an increase in inflammatory markers such as TNFα, Il-1β and CD3e in the wildtype mucosa. While there are some benefits with TB ingestion for barrier properties and microbial composition in the diseased cecum, potentially detrimental effects were noted in the healthy colon.

Keywords: Butyrate; Chloride losing diarrhea; Colon; Inflammatory bowel disease; Microbiome; SLC26A3; Short-chain fatty acids.