FMT from IBS-D Rats Impairs Intestinal Barrier Function and is Associated with Increased Intestinal Benzoic Acid and Ruminococcus Abundance.

Abstract

While the etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is multifactorial, current studies have converged to identify gut microbiota dysbiosis as a principal contributor. This study aimed to elucidate the role of the gut microbiota in IBS-D progression and to uncover the underlying mechanisms. In this study, a rat model of IBS-D was successfully established, characterized by prominent visceral hypersensitivity and diarrhea. To assess the impact of the gut microbiota, recipient rats pretreated with broad-spectrum antibiotics underwent fecal microbiota transplantation (FMT) from IBS-D model rats. The model-microbiota recipient rats (the MR group) developed IBS-D-like symptoms, such as abdominal pain, diarrhea, and depression-like behaviors. Both the IBS-D and MR groups exhibited elevated serum diamine oxidase (DAO) concentrations, reduced intestinal tight junction protein levels, increased serum TNF-α concentrations, upregulated TNF-α mRNA expression, and downregulated IL-10 mRNA expression in the intestine. These findings indicated that the transplanted microbiota disrupted intestinal barrier integrity and triggered low-grade inflammation. Moreover, an elevated abundance of Ruminococcaceae in the gut microbiota was a common feature of both the IBS-D and MR groups. Metabolomic analysis revealed an enrichment in the phenylalanine, tyrosine, and tryptophan biosynthesis pathway in both IBS-D and recipient groups, with benzoic acid being particularly prominent. Pearson correlation analysis demonstrated a strong positive correlation between the Ruminococcus abundance and benzoic acid levels. Together, these findings indicated that FMT robustly recapitulated core IBS-D pathophysiology in recipient rats, and the identified bacteria and metabolites provided novel insights into the pathogenesis of IBS-D.