An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

中文翻译：

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在腹泻型肠易激综合征中，富含梭状芽胞杆菌的微生物群可增强胆汁酸的排泄。

过量的粪便胆汁酸（BAs）被认为是腹泻型肠易激综合症（IBS-D）的机制之一。然而，导致BA过量排泄的因素仍未得到充分研究。鉴于肠道菌群在BA代谢中的重要性，我们假设肠道营养不良可能会导致IBS-D中过量的BA排泄。通过对290名IBS-D患者和89名健康志愿者进行与BA相关的代谢和宏基因组学分析，我们发现24.5％的IBS-D患者表现出粪便中总BA过量分泌和BA转化细菌改变。值得注意的是，梭状芽孢杆菌细菌（如梭状芽孢杆菌）的增加与粪便BAs水平和血清7α-羟基-4-胆甾烯3一（C4）呈正相关，而与血清成纤维细胞生长因子19呈负相关（ FGF19）浓度。此外，用富含梭状芽胞杆菌的IBS-D粪便微生物群或梭状芽孢杆菌定殖分别增强了小鼠血清C4和肝结合的BAs，但降低了回肠FGF19的表达。万古霉素抑制梭状芽胞杆菌产生相反的结果。梭状芽胞杆菌来源的BAs在体外和体内均抑制了肠道FGF19的表达。总之，这项研究表明，富含梭状芽胞杆菌的微生物群会导致IBS-D患者过量的BA排泄，这提供了一种可验证的临床意义的机制假设。梭状芽胞杆菌来源的BAs在体外和体内均抑制了肠道FGF19的表达。总之，这项研究表明，富含梭状芽胞杆菌的微生物群会导致IBS-D患者过量的BA排泄，这提供了一种可验证的临床意义的机制假设。梭状芽胞杆菌来源的BAs在体外和体内均抑制了肠道FGF19的表达。总之，这项研究表明，富含梭状芽胞杆菌的微生物群会导致IBS-D患者过量的BA排泄，这提供了一种可验证的临床意义的机制假设。