Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome
Abstract The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosi...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40552-y |
| _version_ | 1797557863793557504 |
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| author | Lixiang Zhai Haitao Xiao Chengyuan Lin Hoi Leong Xavier Wong Yan Y. Lam Mengxue Gong Guojun Wu Ziwan Ning Chunhua Huang Yijing Zhang Chao Yang Jingyuan Luo Lu Zhang Ling Zhao Chenhong Zhang Johnson Yiu-Nam Lau Aiping Lu Lok-Ting Lau Wei Jia Liping Zhao Zhao-Xiang Bian |
| author_facet | Lixiang Zhai Haitao Xiao Chengyuan Lin Hoi Leong Xavier Wong Yan Y. Lam Mengxue Gong Guojun Wu Ziwan Ning Chunhua Huang Yijing Zhang Chao Yang Jingyuan Luo Lu Zhang Ling Zhao Chenhong Zhang Johnson Yiu-Nam Lau Aiping Lu Lok-Ting Lau Wei Jia Liping Zhao Zhao-Xiang Bian |
| author_sort | Lixiang Zhai |
| collection | DOAJ |
| description | Abstract The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is 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 show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. 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. |
| first_indexed | 2024-03-10T17:23:17Z |
| format | Article |
| id | doaj.art-4761893c769046958a1acdec4f252085 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:23:17Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4761893c769046958a1acdec4f2520852023-11-20T10:16:31ZengNature PortfolioNature Communications2041-17232023-08-0114111410.1038/s41467-023-40552-yGut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndromeLixiang Zhai0Haitao Xiao1Chengyuan Lin2Hoi Leong Xavier Wong3Yan Y. Lam4Mengxue Gong5Guojun Wu6Ziwan Ning7Chunhua Huang8Yijing Zhang9Chao Yang10Jingyuan Luo11Lu Zhang12Ling Zhao13Chenhong Zhang14Johnson Yiu-Nam Lau15Aiping Lu16Lok-Ting Lau17Wei Jia18Liping Zhao19Zhao-Xiang Bian20Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversitySchool of Pharmaceutical Sciences, Health Science Center, Shenzhen UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversitySchool of Chinese Medicine, Hong Kong Baptist UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversityState Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Healthy. School of Environmental and Biological Sciences, Rutgers UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversitySchool of Chinese Medicine, Hong Kong Baptist UniversityDepartment of Computer Science, Hong Kong Baptist UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversityDepartment of Computer Science, Hong Kong Baptist UniversityAcademy of Integrative Medicine, Shanghai University of Traditional Chinese MedicineState Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversitySchool of Chinese Medicine, Hong Kong Baptist UniversitySchool of Chinese Medicine, Hong Kong Baptist UniversitySchool of Chinese Medicine, Hong Kong Baptist UniversityPhenome Research Centre, School of Chinese Medicine, Hong Kong Baptist UniversityDepartment of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Healthy. School of Environmental and Biological Sciences, Rutgers UniversityCentre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist UniversityAbstract The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is 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 show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. 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.https://doi.org/10.1038/s41467-023-40552-y |
| spellingShingle | Lixiang Zhai Haitao Xiao Chengyuan Lin Hoi Leong Xavier Wong Yan Y. Lam Mengxue Gong Guojun Wu Ziwan Ning Chunhua Huang Yijing Zhang Chao Yang Jingyuan Luo Lu Zhang Ling Zhao Chenhong Zhang Johnson Yiu-Nam Lau Aiping Lu Lok-Ting Lau Wei Jia Liping Zhao Zhao-Xiang Bian Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome Nature Communications |
| title | Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| title_full | Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| title_fullStr | Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| title_full_unstemmed | Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| title_short | Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| title_sort | gut microbiota derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome |
| url | https://doi.org/10.1038/s41467-023-40552-y |
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