Huimin Chi1,2, Wa Cao1,3, Ming Zhang4, Donghong Su1,5, Honglian Yang1, Zhe Li1, Chao Li1, Xiaojun She1, Kun Wang1, Xiujie Gao1, Kefeng Ma1, Pengfang Zheng1,2, Xiaofang Li1,6, Bo Cui7,8. 1. Institute of Environmental and Operational Medicine, Chinese Academy of Military Medical sciences, Tianjin, China. 2. School of Public Health and Management, Weifang Medical University, Weifang, China. 3. College of Public Health, North China University of Science and Technology, Tangshan, China. 4. Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China. 5. Zibo Center for Disease Control and Prevention, Zibo, China. 6. School of Public Health and Management, Binzhou Medical University, Yantai, China. 7. Institute of Environmental and Operational Medicine, Chinese Academy of Military Medical sciences, Tianjin, China. iamcuib@sina.com. 8. School of Public Health and Management, Weifang Medical University, Weifang, China. iamcuib@sina.com.
Abstract
BACKGROUND: Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer's disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. METHODS: The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut-brain axis was conducted to explore the underlying pathological mechanisms. RESULTS: Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut-brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. CONCLUSION: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome-gut-brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.
BACKGROUND: Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer's disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. METHODS: The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut-brain axis was conducted to explore the underlying pathological mechanisms. RESULTS: Both WT and APP/PS1mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut-brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. CONCLUSION: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome-gut-brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.
Authors: D Campion; C Dumanchin; D Hannequin; B Dubois; S Belliard; M Puel; C Thomas-Anterion; A Michon; C Martin; F Charbonnier; G Raux; A Camuzat; C Penet; V Mesnage; M Martinez; F Clerget-Darpoux; A Brice; T Frebourg Journal: Am J Hum Genet Date: 1999-09 Impact factor: 11.025