PMID- 37460578 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230720 IS - 2396-8370 (Electronic) IS - 2396-8370 (Linking) VI - 7 IP - 1 DP - 2023 Jul 17 TI - Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice. PG - 36 LID - 10.1038/s41538-023-00212-3 [doi] LID - 36 AB - A high-methionine (HM) diet leads to hyperhomocysteinemia (HHcy), while gastrointestinal tissue is an important site of net homocysteine (Hcy) production. However, the role of the gut microbiota in host HHcy remains obscure. This study aimed to determine whether gut microbiota ablation could alleviate host HHcy and glucose intolerance and reveal the underlying mechanism. The results showed that the HM diet-induced HHcy and glucose intolerance in mice, while antibiotic administration decreased the plasma level of Hcy and reversed glucose intolerance. HM diet increased intestinal epithelial homocysteine levels, while antibiotic treatment decreased intestinal epithelial homocysteine levels under the HM diet. Gut microbiota depletion had no effect on the gene expression and enzyme activity of CBS and BHMT in the livers of HM diet-fed mice. The HM diet altered the composition of the gut microbiota with marked increases in the abundances of Faecalibaculum and Dubosiella, which were also positively correlated with plasma Hcy concentrations. An in-depth analysis of the bacterial cysteine and methionine metabolism pathways showed that the abundances of two homocysteine biosynthesis-related KEGG orthologies (KOs) were markedly increased in the gut microbiota in HM diet-fed mice. Hcy was detected from Dubosiella newyorkensis-cultured supernatant by liquid chromatography-tandem mass spectrometry (LC‒MS) analysis. In conclusion, these findings suggested that the HM diet-induced HHcy and glucose intolerance in mice, by reshaping the composition of the gut microbiota, which might produce and secrete Hcy. CI - (c) 2023. The Author(s). FAU - Li, Wenqiang AU - Li W AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Jia, Yiting AU - Jia Y AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Gong, Ze AU - Gong Z AUID- ORCID: 0000-0002-5247-3948 AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Dong, Zhao AU - Dong Z AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Yu, Fang AU - Yu F AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Fu, Yi AU - Fu Y AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. FAU - Jiang, Changtao AU - Jiang C AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. jiangchangtao@bjmu.edu.cn. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. jiangchangtao@bjmu.edu.cn. AD - Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China. jiangchangtao@bjmu.edu.cn. AD - Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, China. jiangchangtao@bjmu.edu.cn. FAU - Kong, Wei AU - Kong W AUID- ORCID: 0000-0001-6720-6810 AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. kongw@bjmu.edu.cn. AD - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. kongw@bjmu.edu.cn. LA - eng GR - 81730010/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 91539203/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 81921001/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 91839302/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 31930056/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 81900261/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article DEP - 20230717 PL - England TA - NPJ Sci Food JT - NPJ science of food JID - 101739627 PMC - PMC10352305 COIS- The authors declare no competing interests. EDAT- 2023/07/18 01:09 MHDA- 2023/07/18 01:10 PMCR- 2023/07/17 CRDT- 2023/07/17 23:21 PHST- 2022/12/13 00:00 [received] PHST- 2023/07/12 00:00 [accepted] PHST- 2023/07/18 01:10 [medline] PHST- 2023/07/18 01:09 [pubmed] PHST- 2023/07/17 23:21 [entrez] PHST- 2023/07/17 00:00 [pmc-release] AID - 10.1038/s41538-023-00212-3 [pii] AID - 212 [pii] AID - 10.1038/s41538-023-00212-3 [doi] PST - epublish SO - NPJ Sci Food. 2023 Jul 17;7(1):36. doi: 10.1038/s41538-023-00212-3.