Escherichia coli Nissle Improves Short-Chain Fatty Acid Absorption and Barrier Function in a Mouse Model for Chronic Inflammatory Diarrhea.

Abstract

Background: Defects in SLC26A3, the major colonic Cl-/HCO3- exchanger, result in chloride-rich diarrhea, a reduction in short-chain fatty acid (SCFA)-producing bacteria, and a high incidence of inflammatory bowel disease in humans and in mice. Slc26a3-/- mice are, therefore, an interesting animal model for spontaneous but mild colonic inflammation and for testing strategies to reverse or prevent the inflammation. This study investigates the effect of Escherichia coli Nissle (EcN) application on the microbiome, SCFA production, barrier integrity, and mucosal inflammation in slc26a3-/- mice.

Methods: In vivo fluid absorption and bicarbonate secretion were assessed in the gut of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion with 100 mM sodium acetate. Age-matched slc26a3+/+ and slc26a3-/- mice were intragastrically gavaged twice daily with 2 × 108 CFU/100 µL of EcN for 21 days. Body weight and stool water content were assessed daily, and stool and tissues were collected for further analysis.

Results: Addition of sodium acetate to the lumen of the proximal colon significantly increased fluid absorption and luminal alkalinization in the slc26a3-/- mice. Gavage with EcN resulted in a significant increase in SCFA levels and the expression of SCFA transporters in the slc26a3-/- cecum, the predominant habitat of EcN in mice. This was accompanied by an increase in mucus-producing goblet cells and a decrease in the expression of inflammatory markers as well as host defense antimicrobial peptides. EcN did not improve the overall diversity of the luminal microbiome but resulted in a significant increase in SCFA producers Lachnospiraceae and Ruminococcaceae in the slc26a3-/- feces.

Conclusions: These findings suggest that EcN is able to proliferate in the inflamed cecum, resulting in increased microbial SCFA production, decreased inflammation, and improved gut barrier properties. In sufficient dosage, probiotics may thus be an effective anti-inflammatory strategy in the diseased gut.