Sex-Dependent Microbial and Host Profiles Following Fecal Microbiota and Bifidobacterium longum Treatment in Stress-Induced Gut Dysbiosis.
BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress. METHODS: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction. RESULTS: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats. CONCLUSIONS: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.