Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Zhai, Lixiang; Huang, Chunhua; Ning, Ziwan; Zhang, Yijing; Zhuang, Min; Yang, Weng Lang; Wang, Xiaolei; Wang, Jingjing; Zhang, Lu; Xiao, Haitao; Zhao, Ling; Asthana, Pallavi; Lam, Yan Y.; Chow, Chi Fung Willis; Huang, Jian‐Dong; Yuan, Shuofeng; Chan, Kui Ming; Yuan, Chun‐Su; Lau, Johnson Y. N.; Wong, Hoi Leong Xavier; Bian, Zhaoxiang

doi:10.1016/j.chom.2022.11.006

Cited by 73 publications

(43 citation statements)

References 41 publications

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“…R. gnavus was significantly more abundant in patients with diarrhoea-predominant IBS (IBS-D). This was associated with peripheral 5-hydroxytryptamine (5-HT) and severe symptoms, as also shown in R. gnavus mono-colonized mice (Zhai et al 2023 ) (see section on the 'Molecular mediators underpinning the effect of R. gnavus on health and disease'). By integrating multiple data layers, purine metabolism was identified as a novel host–microbial metabolic pathway in IBS (Mars et al 2020 ).…”

Section: Association Between R Gnavus and Diseasesmentioning

confidence: 64%

Ruminococcus gnavus: friend or foe for human health

Crost

Coletto

Bell

et al. 2023

FEMS Microbiology Reviews

102

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Ruminococcus gnavus was first identified in 1974 as a strict anaerobe in the gut of healthy individuals, and for several decades, its study has been limited to specific enzymes or bacteriocins. With the advent of metagenomics, R. gnavus has been associated both positively and negatively with an increasing number of intestinal and extra-intestinal diseases from inflammatory bowel diseases to neurological disorders. This prompted renewed interest in understanding the adaptation mechanisms of R. gnavus to the gut, and the molecular mediators affecting its association with health and disease. From ca. 250 publications citing R. gnavus since 1990, 94% were published in the last 10 years. In this review, we describe the biological characterisation of R. gnavus, its occurrence in the infant and adult gut microbiota and the factors influencing its colonisation of the gastrointestinal tract; we also discuss the current state of our knowledge on its role in host health and disease. We highlight gaps in knowledge and discuss the hypothesis that differential health outcomes associated with R. gnavus in the gut are strain and niche specific.

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Section: Association Between R Gnavus and Diseasesmentioning

confidence: 64%

Ruminococcus gnavus: friend or foe for human health

Crost

Coletto

Bell

et al. 2023

FEMS Microbiology Reviews

102

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“…One approach by which probiotics impact the host immune system is through the microbial metabolism that arises from intestinal microbiota catabolism ( 36 – 39 ): e.g., functional metagenomic studies have identified the associations between host proinflammatory cytokines and microbial tryptophan and palmitoleic acid metabolic pathways ( 37 , 38 , 40 – 42 ). Moreover, previous studies have illustrated that the gut microbiota and metabolites activate the host immune system, thereby increasing the expression of endocrine peptides and promoting host metabolic homeostasis ( 37 , 43 , 44 ). In addition, characterization of stable and changeable genetic components in the gut microbiome is crucial for further understanding the role of the gut microbiome in human health and phenotypic changes ( 45 ), which has rarely been investigated in probiotic studies.…”

Section: Introductionmentioning

confidence: 99%

Change in the Gut Microbiome and Immunity by Lacticaseibacillusrhamnosus Probio-M9

et al. 2023

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“…TAAR1 is an amine-activated G proteincoupled receptor that is activated by gut microbes-derived aromatic trace amines including tryptamine, phenethylamine and tyramine in gut 25 . In contrast, only tryptamine and phenethylamine but not tyramine was found altered in diabetic monkeys, patients with T2D (Figure .S6C-D) or IBS 15 . An endogenous activator (3-iodothyronamine) of TAAR1 has recently been shown to improve glycemic control by promoting insulin secretion in beta-cells 26 .…”

Section: Discussionmentioning

confidence: 90%

“…Interestingly, we found fasting blood glucose, triglyceride, and triglycerideglucose (TyG) index are all significantly increased in IBS patients (p<0.001 in all cases, Figure.1A-C), suggesting IBS patients have higher diabetes risks compared with healthy controls. We then analyzed the association between gut microbes and insulin resistance in HC and IBS participants using their shotgun metagenomic sequencing data 14 Given that R. gnavus is a primary gut microbe that is capable of decarboxylating tryptophan and phenylalanine into tryptamine and phenethylamine as shown by our previous findings 15 , elevated fecal tryptamine and phenethylamine levels were found along with impaired glucose tolerance and insulin sensitivity in germ-free mice colonized with R. gnavus (p<0.01 in all cases, Figure .1G-H). To further investigate whether tryptamine and phenethylamine produced by R. gnavus-derived decarboxylase (TDC) impair insulin sensitivity in vivo, we ectopically expressed TDC gene from R. gnavus (ATCC 29149) in a commensal gram-positive bacterium Lactobacillus casei, which does not produce tryptamine or phenethylamine.…”

Section: R Gnavus Is Positively Associated With Insulin Resistance In...mentioning

confidence: 99%

Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome

Zhai

Xiao

Lin

et al. 2023

Preprint

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The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota has been causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we showed that human gut bacterium Ruminococcus gnavus play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. Monoassociation of R. gnavus impaired insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impaired insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect was mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Moreover, we showed levels of R. gnavus, tryptamine and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.

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Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Cited by 73 publications

References 41 publications

Ruminococcus gnavus: friend or foe for human health

Ruminococcus gnavus: friend or foe for human health

Change in the Gut Microbiome and Immunity by Lacticaseibacillusrhamnosus Probio-M9

Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome

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