Background Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional bowel disorder closely associated with gut microbiota dysbiosis and gut-brain axis dysfunction. However, effective treatment options remain limited. In this study, we investigated the therapeutic effects and underlying mechanisms of an extract derived from the pulp of Rosa roxburghii Tratt after co-fermentation with Saccharomyces cerevisiae and Bacillus subtilis (referred to as FRRTP) in a mouse model of IBS-D. Methods Rosa roxburghii Tratt pulp Co-fermented with Saccharomyces cerevisiae and Bacillus subtilis , followed by extraction, was analyzed by UPLC-Q-Exactive Orbitrap-rbitrap OrExactive Oron, was ouse model of IBS-D. This study, we investigated the therapeutic effects and underlying mechanisms of an extract derived from the pulp of t version, please let us know that does nointragastric Senna Folium extract. After FRRTP intervention, diarrhea symptoms, abdominal withdrawal reflex, behavioral tests, colon and brain histopathology, inflammatory cytokines, and gut-brain neurotransmitters were evaluated. Gut microbiota was analyzed by 16S rRNA sequencing. Untargeted metabolomics was performed on serum and colon samples, and AFADESI-MSI spatial metabolomics was used to map metabolic alterations in the brain. Results Co-fermentation significantly increased the variety and content of bioactive components (e.g., flavonoids and polyphenols) in Rosa roxburghii Tratt pulp. Compared with the model group, FRRTP alleviated diarrhea, visceral hypersensitivity, colonic damage, and brain histopathological damage, reduced TNF-α, IL-6, and IL-1β levels; modulated brain-gut neuropeptides (5-HT, SP, VIP); and improved anxiety-like behaviors. 16S rRNA sequencing revealed that FRRTP reversed gut microbiota dysbiosis by increasing beneficial bacteria and reducing the proportion of pathogenic bacteria. Metabolomics showed that FRRTP regulated tryptophan, purine, and glycerophospholipid pathways, spatial metabolomics confirmed that FRRTP ameliorated the disturbed cerebral distribution of 5-HT, tryptophan, glycerophosphocholine, dopamine, and adrenaline. Conclusion Our findings demonstrate that FRRTP alleviates IBS-D symptoms in mice by modulating the gut microbiota and correcting metabolic disturbances, supporting its potential development as a functional food or therapeutic agent for IBS-D.
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