Differences in the Plasma Bile Acid‐Gut Microbiota Axis Between IBS‐D and IBS‐C

ABSTRACT Background Irritable bowel syndrome with constipation (IBS‐C) and diarrhea (IBS‐D) exhibit highly divergent clinical manifestations. This study aims to investigate the correlation between IBS‐C and IBS‐D. Methods All participants provided fecal samples and completed IBS‐SSS, IBS‐QOL, and GSRS. Fecal bacterial composition was analyzed via custom V4‐region 16S rRNA amplicon sequencing on the Illumina NovaSeq 6000 platform, while bile acids were quantified using liquid chromatography–tandem mass spectrometry (LC–MS). Key Results Patients with IBS‐D reported significantly higher frequency and severity of diarrhea and abdominal pain. Conversely, IBS‐C patients experienced more severe bloating and constipation than IBS‐D patients. Compared to HCs, total bile acids, primary bile acids, secondary bile acids, conjugated bile acids, and unconjugated bile acids were elevated in IBS‐D but reduced in IBS‐C. The gut microbiota composition of both IBS‐D and IBS‐C patients differed significantly from that of HCs. Differential species in the IBS‐D group were primarily associated with Prevotella and Ruminococcaceae, those in the IBS‐C group were mainly concentrated in Bacteroides and Clostridium, and differential species in the HCs group were primarily found in Ruminococcus. Abundances of Clostridiaceae and Bacteroides correlated negatively with plasma chenodeoxycholic acid and cholic acid, respectively, while Clostridium correlated negatively with ursodeoxycholic acid (UDCA). Ruminococcus correlated positively with isodeoxycholic acid. Conclusions Alterations in the bile acid–gut microbiota axis are closely related to the distinct clinical presentations of IBS‐C and IBS‐D. IBS‐D is characterized by a decreased abundance of Ruminococcus and Clostridium, alongside increased bile acid secretion and reduced reabsorption, which primarily contribute to the observed differences.