Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation.
Level 5 - mechanism / opinion, no new human data
Preclinical animal experimentation (DSS colitis mouse model) combined with correlative observational profiling of human fecal samples.
PubMed 39806416 · doi:10.1186/s12967-024-05873-6
What was done
Researchers evaluated bile acid profiles (via UPLC-MS) and microbial composition (via 16S rRNA sequencing and metagenomic profiling) in fecal samples from patients with inflammatory bowel disease (IBD) and mice with dextran sulfate sodium (DSS)-induced colitis, with and without antibiotic treatment. Colonic tissue from DSS-treated mice was analyzed using histology, qPCR, and Western blotting to evaluate mucosal barrier integrity and inflammatory signaling pathways. Lithocholic acid (LCA) was administered via oral gavage in mice to test its direct effect on colonic inflammation.
What was found
The abstract reports no numerical values, effect sizes, sample sizes, or p-values. Qualitatively, both IBD patients and DSS-colitis mice showed altered gut microbiota and bile acid profiles, with LCA identified via multivariate analysis as the primary bile acid associated with colonic inflammation and mucosal barrier disruption. In mice, LCA supplementation exacerbated colitis progression via activation of the S1PR2/NF-κB p65 signaling pathway. An unclassified genus within the Prevotellaceae family was enriched in DSS-colitis mice and correlated positively with bile acid biosynthesis pathways and colonic LCA levels.
Why it matters
This study links Prevotellaceae-associated secondary bile acid metabolism, specifically LCA, to colonic barrier dysfunction and inflammation, highlighting the S1PR2/NF-κB pathway as a potential mechanistic target in colitis.
Limits
The abstract reports no quantitative data, sample sizes, patient baseline characteristics, or statistical confidence intervals. Interventional mechanism experiments were conducted in a chemically induced mouse model, which may not capture the full heterogeneity of human IBD.
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- supports Excessive accumulation of secondary bile salts, produced when gut microbes convert primary bile, can cause inflammation in the large intestine.