A <i>Clostridia</i>-rich microbiota contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome

Zhao, Ling; Yang, Weng Lang; Chen, Y; Huang, Fengjie; Lu, Lingling; Lin, Chin‐Teng; Huang, Tao; Ning, Ziwan; Zhai, Lixiang; Ll, Zhong; W, Lam; Yang, Zhen; Zhang, X; Cheng, Chung Wah; Han, Ling; Q, Qiu; Shang, Xuan; Huang, Run‐Yue; Z, Ren; Chen, D; Sun, Shunrong; El‐Nezami, Hani; Lü, Aiping; Fang, Xiaodong; Wang, Jia; Bian, Zhao Xiang

doi:10.1101/630350

Cited by 3 publications

(1 citation statement)

References 62 publications

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“…On the other hand, UDCA has also been described as an FXR antagonist able to increase BA synthesis and reduce FGF19 levels in obese patients (306). Similarly, a Clostridia-rich microbiota and their BA metabolites, including UDCA, were shown to suppress intestinal FGF19 expression contributing to excessive BA excretion in patients with diarrhea-predominant irritable bowel syndrome (480). Remodeling of the gut microbiota and alteration of the BA profile also takes place after chronic alcohol consumption (159).…”

Section: F1 the Gut Microbiome Shapes The Ba Poolmentioning

confidence: 99%

Molecular physiology of bile acid signaling in health, disease, and aging

Perino

Demagny

Velázquez-Villegas

et al. 2021

Physiological Reviews

248

193

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Over the last two decades, bile acids (BAs) have become established as important signaling molecules that enable fine-tuned inter-tissue communication from the liver, their site of production, over the intestine, where they are modified by the gut microbiota, to virtually any organ, where they exert their pleiotropic physiological effects. The chemical variety of BAs, to a large extent determined by the gut microbiome, also allows for a complex fine-tuning of adaptive responses in our body. This review provides an overview of the mechanisms by which BA receptors coordinate several aspects of physiology and highlights new therapeutic strategies for diseases underlying pathological BA signaling.

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Section: F1 the Gut Microbiome Shapes The Ba Poolmentioning

confidence: 99%

Molecular physiology of bile acid signaling in health, disease, and aging

Perino

Demagny

Velázquez-Villegas

et al. 2021

Physiological Reviews

248

193

View full text Add to dashboard Cite

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Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Zhai

Huang

Ning

et al. 2022

Preprint

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SummaryDespite the strong association between gut microbial dysbiosis, serotonin (5-HT) dysregulation and diarrhea-predominant irritable bowel syndrome (IBS-D), the mechanism by which changes in the gut microbiota contribute to the pathogenesis of IBS-D, particularly the role of dysregulated 5-HT production, remains unclear. The present study identified Ruminococcus gnavus in the human gut microbiota as a key risk factor of IBS-D. R. gnavus was significantly enriched in IBS-D patients and exhibited positive correlation with serum 5- HT level and severity of diarrhea symptoms. We showed that R. gnavus induced diarrhea-like symptoms in mice by promoting microbial shunting of essential aromatic amino acids to aromatic trace amines including phenethylamine and tryptamine, thereby stimulating the biosynthesis of peripheral 5-HT, a potent stimulator for gastrointestinal transit. This study identify gut-microbial metabolism of dietary amino acids as a cause of IBS-D and lays a foundation for developing novel therapeutic target for the treatment of IBS-D.Graphical abstract

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Gut microbiota-derived tryptamine impairs insulin sensitivity

Zhai

Xiao

Lin

et al. 2022

Preprint

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Gut-microbiota plays a pivotal role in development of type 2 diabetes (T2D), yet the molecular mechanism remains elusive. Here, we show that tryptamine, a microbial metabolite of tryptophan, impairs glucose tolerance and insulin sensitivity. Tryptamine presents a higher level in monkeys with spontaneous diabetes and human with T2D and positively correlated with the glucose tolerance. In parallel, tryptamine level was suppressed by dietary fibers intervention in T2D subjects and negatively correlated with improvement of glucose tolerance. The inhibitory effect of tryptamine on insulin signaling as shown was dependent on a trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Monoassociation of T2D-associated tryptamine-producing bacteria Ruminococcus gnavus impairs insulin sensitivity in pseudo germ-free mice. Our findings indicate gut microbiota-derived tryptamine contributes to the development of insulin resistance in T2D and may serve as a new target for intervention.

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A Clostridia-rich microbiota contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome

Cited by 3 publications

References 62 publications

Molecular physiology of bile acid signaling in health, disease, and aging

Molecular physiology of bile acid signaling in health, disease, and aging

Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Gut microbiota-derived tryptamine impairs insulin sensitivity

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