Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure
Fat mass and obesity-associated protein (FTO) is the key demethylase that reverses the abnormally altered N6-methyladenosine (m6A) modification in eukaryotic cells under environmental pollutants exposure. Arsenic is an environmental metalloid and can cause severe symptoms in human mainly through dri...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2438471 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588850770214912 |
|---|---|
| author | Ruonan Chen Xiaoqin Chai Yunxiao Zhang Tianxiu Zhou Yinyin Xia Xuejun Jiang Bo Lv Jun Zhang Lixiao Zhou Xin Tian Ruonan Wang Lejiao Mao Feng Zhao Hongyang Zhang Jun Hu Jingfu Qiu Zhen Zou Chengzhi Chen |
| author_facet | Ruonan Chen Xiaoqin Chai Yunxiao Zhang Tianxiu Zhou Yinyin Xia Xuejun Jiang Bo Lv Jun Zhang Lixiao Zhou Xin Tian Ruonan Wang Lejiao Mao Feng Zhao Hongyang Zhang Jun Hu Jingfu Qiu Zhen Zou Chengzhi Chen |
| author_sort | Ruonan Chen |
| collection | DOAJ |
| description | Fat mass and obesity-associated protein (FTO) is the key demethylase that reverses the abnormally altered N6-methyladenosine (m6A) modification in eukaryotic cells under environmental pollutants exposure. Arsenic is an environmental metalloid and can cause severe symptoms in human mainly through drinking water. However, there is no specific treatment for its toxic effects due to the uncovered mechanisms. We previously revealed that exposure to arsenic increased the level of m6A via down-regulation of FTO, which might serve as a potential target for intervention against arsenic-related disorders. In this study, our results demonstrated that chronic exposure to arsenic significantly disrupted the intestinal barrier and microenvironment. Also, this administration resulted in the enhancement of m6A modification and the reduction of FTO expression in the intestine. By using both CRISPR/Cas9-based FTO knock-in strategy and adeno-associated virus (AAV)-mediated overexpression of FTO in the intestine, we established for the first time that up-regulation of FTO remarkably ameliorated arsenic-induced disruption of intestinal barriers and altered microenvironment of mice. We also firstly identified a dominant gut microbial species, Desulfovibrio fairfieldensis, which was sharply reduced in arsenic-exposed mice, was able to proceed arsenic-induced neurobehavioral impairments by declining the levels of its major metabolite hydrogen sulfide. Administration of Desulfovibrio fairfieldensis could significantly alleviate the neurotoxicity of arsenic. Intriguingly, the beneficial effects of FTO against arsenic neurotoxicity possibly occurred through a novel gut–brain communication via Desulfovibrio fairfieldensis and its produced hydrogen sulfide. Collectively, these findings will provide new ideas for understanding the mechanisms of arsenic-induced toxic effects from a gut–brain communication perspective, and will assist the development of explicit intervention strategy via regulation of a new potential target FTO for prevention and treatment against arsenic-related both intestinal and neurological disorders. |
| format | Article |
| id | doaj-art-98c8194f5b5c40e4ba7ccfd8d3770156 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-98c8194f5b5c40e4ba7ccfd8d37701562025-01-24T13:26:19ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2024.2438471Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposureRuonan Chen0Xiaoqin Chai1Yunxiao Zhang2Tianxiu Zhou3Yinyin Xia4Xuejun Jiang5Bo Lv6Jun Zhang7Lixiao Zhou8Xin Tian9Ruonan Wang10Lejiao Mao11Feng Zhao12Hongyang Zhang13Jun Hu14Jingfu Qiu15Zhen Zou16Chengzhi Chen17Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaCenter of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaResearch Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of ChinaResearch Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaFat mass and obesity-associated protein (FTO) is the key demethylase that reverses the abnormally altered N6-methyladenosine (m6A) modification in eukaryotic cells under environmental pollutants exposure. Arsenic is an environmental metalloid and can cause severe symptoms in human mainly through drinking water. However, there is no specific treatment for its toxic effects due to the uncovered mechanisms. We previously revealed that exposure to arsenic increased the level of m6A via down-regulation of FTO, which might serve as a potential target for intervention against arsenic-related disorders. In this study, our results demonstrated that chronic exposure to arsenic significantly disrupted the intestinal barrier and microenvironment. Also, this administration resulted in the enhancement of m6A modification and the reduction of FTO expression in the intestine. By using both CRISPR/Cas9-based FTO knock-in strategy and adeno-associated virus (AAV)-mediated overexpression of FTO in the intestine, we established for the first time that up-regulation of FTO remarkably ameliorated arsenic-induced disruption of intestinal barriers and altered microenvironment of mice. We also firstly identified a dominant gut microbial species, Desulfovibrio fairfieldensis, which was sharply reduced in arsenic-exposed mice, was able to proceed arsenic-induced neurobehavioral impairments by declining the levels of its major metabolite hydrogen sulfide. Administration of Desulfovibrio fairfieldensis could significantly alleviate the neurotoxicity of arsenic. Intriguingly, the beneficial effects of FTO against arsenic neurotoxicity possibly occurred through a novel gut–brain communication via Desulfovibrio fairfieldensis and its produced hydrogen sulfide. Collectively, these findings will provide new ideas for understanding the mechanisms of arsenic-induced toxic effects from a gut–brain communication perspective, and will assist the development of explicit intervention strategy via regulation of a new potential target FTO for prevention and treatment against arsenic-related both intestinal and neurological disorders.https://www.tandfonline.com/doi/10.1080/19490976.2024.2438471ArsenicGut–brain communicationFTODesulfovibrio fairfieldensisNeurobehavior impairments |
| spellingShingle | Ruonan Chen Xiaoqin Chai Yunxiao Zhang Tianxiu Zhou Yinyin Xia Xuejun Jiang Bo Lv Jun Zhang Lixiao Zhou Xin Tian Ruonan Wang Lejiao Mao Feng Zhao Hongyang Zhang Jun Hu Jingfu Qiu Zhen Zou Chengzhi Chen Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure Gut Microbes Arsenic Gut–brain communication FTO Desulfovibrio fairfieldensis Neurobehavior impairments |
| title | Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure |
| title_full | Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure |
| title_fullStr | Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure |
| title_full_unstemmed | Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure |
| title_short | Novel role of FTO in regulation of gut–brain communication via Desulfovibrio fairfieldensis-produced hydrogen sulfide under arsenic exposure |
| title_sort | novel role of fto in regulation of gut brain communication via desulfovibrio fairfieldensis produced hydrogen sulfide under arsenic exposure |
| topic | Arsenic Gut–brain communication FTO Desulfovibrio fairfieldensis Neurobehavior impairments |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2438471 |
| work_keys_str_mv | AT ruonanchen novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT xiaoqinchai novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT yunxiaozhang novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT tianxiuzhou novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT yinyinxia novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT xuejunjiang novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT bolv novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT junzhang novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT lixiaozhou novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT xintian novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT ruonanwang novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT lejiaomao novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT fengzhao novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT hongyangzhang novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT junhu novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT jingfuqiu novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT zhenzou novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure AT chengzhichen novelroleofftoinregulationofgutbraincommunicationviadesulfovibriofairfieldensisproducedhydrogensulfideunderarsenicexposure |