Bian Zhaoxiang,
Hong Kong Baptist University, Hong Kong
Title: Clostridium-enriched enterotype contribute to bile acid oversynthesis in patients with diarrhea-predominant irritable bowel syndrome
Biography
Biography: Bian Zhaoxiang,
Abstract
Bile acid (BA) overexcretion, strongly linking with the severity of bowel symptoms, affects a considerable population of diarrhea-predominant irritable bowel syndrome (IBS-D), Some genetic and metabolic mechanisms derived from the host have been documented, however the role of gut microbiota has received little attention. To investigate gutmicrobiota and its effect on BA metabolism in IBS-D, a series of metabolic and microbial experiments were performed from bedside to bench. Fecal metagenomic analysis identified a specific enterotype characterized by enrichment of Clostridium in IBS-D cases with BA overexcretion. Abundant Clostridium species showed positive association with human fecal total BA and serum C4 levels, but reversely correlated with serum FGF19. Further, mouse experiments with bacterial manipulation found that enrichment of Clostridium species in the cecal lumens leads to elevation of fecal total BA level and taurine-conjugated BA contents in the liver and ileal contents, along with differential expressions ofhepatic BA synthetase CYP7A1 and ileal feedback regulator FGF15. Mechanistic analyses revealed such microbiotadriven BA synthetic dysregulation is involved in inhibition of FXR-mediated feedback signaling. This study discloses the potential contribution of Clostridium-enriched enterotype in BA overexcretion in IBS-D and also suggest the importance of enterotype classification in pathogenesis and diagnosis for IBS.