Gut最新文献

Background: Dysosmobacter welbionis is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from myo-inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited.

Objective: To assess population-level distribution, relative abundance and strain diversity of D. welbionis in humans, and to elucidate its metabolic capacity to ferment myo-inositol into butyrate.

Design: We analysed several human cohorts for associations with liver health and evaluated D. welbionis J115^T supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined ¹³C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics.

Results: We found that D. welbionis and two related species (D. hominis and D. segnis) are prevalent gut bacteria in the human gut. D. welbionis abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with D. welbionis J115^T improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical myo-inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full myo-inositol fermentation pathway.

Conclusion: D. welbionis possesses a unique, conserved route to convert dietary myo-inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.

Background: Postdischarge morbidity and mortality is high in acute pancreatitis (AP) and pathophysiological mechanisms remain poorly understood.

Objectives: We aim to investigate the composition of gut microbiota and clinical long-term outcomes of prospectively enrolled patients with AP to predict postdischarge complications.

Design: In this long-term follow-up study, we analysed clinical and microbiome data of 277 patients from the prospective multicentre Pancreatitis-Microbiome As Predictor of Severity trial. The primary endpoint was the association of the microbial composition with postdischarge mortality, recurrent AP (RAP), progression to chronic pancreatitis, pancreatic exocrine insufficiency, diabetes mellitus (DM) and pancreatic ductal adenocarcinoma.

Results: Buccal (n=238) and rectal (n=249) swabs were analysed by 16S rRNA and metagenomics sequencing using Oxford Nanopore Technologies. Median follow-up was 2.8 years. Distance-based redundancy analysis with canonical analysis of principal coordinates showed significant differences for β-diversity (Bray-Curtis) for postdischarge mortality (p=0.04), RAP (p=0.02) and DM (p=0.03). A ridge regression model including 11 differentially abundant species predicted postdischarge DM with an area under the receiving operating characteristic of 94.8% and 86.2% in the matched and entire cohort, respectively. Using this classifier, a positive predictive value of 66.6%, a negative predictive value of 96% and an accuracy of 95% was achieved.

Conclusion: Our data indicate that the admission microbiome of patients with AP correlates with postdischarge complications independent from multiple risk factors such as AP severity, smoking or alcohol. Microbiota at admission show excellent capacity to predict postdischarge DM and may thus open new stratification tools for a tailored risk assessment in the future.

Trial registration number: NCT04777812.