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- W3023187410 abstract "Background An excess of fecal bile acids (BAs) is thought to be one of the peripheral mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remains unclear. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. Methods Metabolomic and metagenomic analyses were performed of specimens from 290 IBS-D patients and 89 healthy volunteers. By transplanting human microbiota and manipulating specific bacterial species in mice, the effects of microbiota on host BA metabolism were assessed at metabolic, genetic and protein levels. Effects of individual and mixed BAs on enterohepatic feedback pathways were also tested in vitro and in vivo. Results Total fecal BAs were excessively excreted in 71 of 290 IBS-D patients (grouped as BA+IBS-D) who also have excessive 7α-hydroxy-4-cholesten-3-one (C4) but deficient fibroblast growth factor 19 (FGF19) in sera (Figure 1A-C. The association of clostridia rich microbiota with BA synthesis and excretion in IBS d patients a the histogram of the distribution of total fecal BA level in recruited subjects b c concentrations of C4). Their fecal metagenomes showed increased abundances of Clostridia and BA-transforming genomes (hdhA and bais). The increase of Clostridia (e.g.Clostridium) was positively associated with the levels of fecal BAs and serum C4, while being negatively correlated with serum FGF19 (Figure 1D, E). However, there is no big difference in BA profile and BA-transforming microbiome found in other IBS-D patients with normal BA excretion (grouped as BA-IBS-D) relative to controls. Further, transplantation of Clostridia-rich microbiota from IBS-D donors and introduction of a BA-transforming Clostridium species both enhanced levels of serum C4 and hepatic conjugated BAs in mice and reduced ileal FGF19 expression. Inhibition of Clostridium species by vancomycin yielded opposite findings. Moreover, Clostridia-derived BAs, like conjugated and free ursodeoxycholic acid, were also found to be significantly suppressed intestinal FGF19 expression in vitro and in vivo. Conclusions The Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients. This study provided the basis for more precise clinical diagnosis and management for IBS-D." @default.
- W3023187410 created "2020-05-13" @default.
- W3023187410 creator A5086339442 @default.
- W3023187410 date "2019-06-01" @default.
- W3023187410 modified "2023-09-24" @default.
- W3023187410 title "IDDF2019-ABS-0182 A clostridia-rich enterotype contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome" @default.
- W3023187410 doi "https://doi.org/10.1136/gutjnl-2019-iddfabstracts.34" @default.
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