Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice
Abstract 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 coul...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | npj Science of Food |
| Online Access: | https://doi.org/10.1038/s41538-023-00212-3 |
| _version_ | 1797773966170914816 |
|---|---|
| author | Wenqiang Li Yiting Jia Ze Gong Zhao Dong Fang Yu Yi Fu Changtao Jiang Wei Kong |
| author_facet | Wenqiang Li Yiting Jia Ze Gong Zhao Dong Fang Yu Yi Fu Changtao Jiang Wei Kong |
| author_sort | Wenqiang Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T22:13:07Z |
| format | Article |
| id | doaj.art-970d54abeeac4f38a785f800ecdf0871 |
| institution | Directory Open Access Journal |
| issn | 2396-8370 |
| language | English |
| last_indexed | 2024-03-12T22:13:07Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Science of Food |
| spelling | doaj.art-970d54abeeac4f38a785f800ecdf08712023-07-23T11:27:29ZengNature Portfolionpj Science of Food2396-83702023-07-017111210.1038/s41538-023-00212-3Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in miceWenqiang Li0Yiting Jia1Ze Gong2Zhao Dong3Fang Yu4Yi Fu5Changtao Jiang6Wei Kong7Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterAbstract 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.https://doi.org/10.1038/s41538-023-00212-3 |
| spellingShingle | Wenqiang Li Yiting Jia Ze Gong Zhao Dong Fang Yu Yi Fu Changtao Jiang Wei Kong Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice npj Science of Food |
| title | Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice |
| title_full | Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice |
| title_fullStr | Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice |
| title_full_unstemmed | Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice |
| title_short | Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice |
| title_sort | ablation of the gut microbiota alleviates high methionine diet induced hyperhomocysteinemia and glucose intolerance in mice |
| url | https://doi.org/10.1038/s41538-023-00212-3 |
| work_keys_str_mv | AT wenqiangli ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT yitingjia ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT zegong ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT zhaodong ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT fangyu ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT yifu ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT changtaojiang ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice AT weikong ablationofthegutmicrobiotaalleviateshighmethioninedietinducedhyperhomocysteinemiaandglucoseintoleranceinmice |