E. coli Nissle improves short-chain fatty acid absorption, microbial composition, and gut barrier function in the inflamed cecum ofslc26a3−/− mice

Physiology in Focus 2024 (Northumbria University, UK) (2024) Proc Physiol Soc 59, C28

Oral Communications: E. coli Nissle improves short-chain fatty acid absorption, microbial composition, and gut barrier function in the inflamed cecum ofslc26a3−/− mice

Zhenghao Ye1, Qinghai Tan1, Sabrina Woltemate1, Xinjie Tan1, Dorothee Römermann1, Guntram Grassl1, Marius Vital1, Ursula Seidler1, Archana Kini1,

1Hannover Medical School Hannover Germany, 2Tongji Medical School Wuhan China, 3Zhejiang University Medical School Hangzhou China,

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Background

Defects in SLC26A3, the major colonic Cl/HCO3 exchanger, result in chloride-rich diarrhea, a reduction in short-chain fatty acids (SCFA) producing bacteria, and a high incidence of inflammatory bowel disease (IBD) 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 E. 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 100mM sodium acetate. Age-matched slc26a3+/+ and slc26a3-/- mice (13 wt and 12 ko) were intragastrically gavaged twice daily with 2×108 CFU/100µL of EcN for 21 days. Body weight and stool water content were assessed daily, stool and tissues were collected for further analysis. The data was analysed using Graphpad Prism Version 8.0.2. The unpaired Student´s was used for parametric data with normal distribution or non-parametric Mann-Whitney U test for the comparisons within genotypes and/or between control and EcN-treated groups. For the microbial 16s rRNA gene analysis, the analysis, alpha-diversities, and non-metric multidimensional scaling (NMDS) based on relative abundance data were conducted using the phyloseq package (McMurdie & Holmes, PlosOne 2013).

Results

Luminal addition of sodium acetate significantly increased both fluid absorption and luminal alkalinization in the slc26a3-/- mice. Gavage with EcN resulted in significantly improving overall SCFA levels and the expression of its transporters primarily in the slc26a3-/- cecum, the predominant habitat of EcN in mice (n=12-13, p<0.05). This was accompanied by an increase in mucus producing goblet cells, a decrease in the expression of inflammatory markers as well as of host defense anti-microbial 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 (n=7 for slc26a3+/+ and slc26a3-/- w/o EcN: n=12 for slc26a3+/+ and n=13 for slc26a3-/-, p<0.05.

Conclusions: These findings suggest that EcN is able to proliferate in the inflamed cecum of the slc26a3-/- mice, 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.



Where applicable, experiments conform with Society ethical requirements.

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