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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
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