Chang WY, Qin QZ, Li XT, Wang JJ, Chen Y, Ruan HQ, Qu YN, Jiang XX, He HX. Modulating oral microbiota ameliorates hypobaric hypoxia-induced anxiety- and depression-like behaviors in mice. World J Psychiatry 2025; 15(6): 104809 [DOI: 10.5498/wjp.v15.i6.104809]
Corresponding Author of This Article
Hui-Xia He, Department of Stomatology, First Medical Center of Chinese PLA General Hospital and Medical School of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. hehuixia@301hospital.com.cn
Research Domain of This Article
Medicine, General & Internal
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Wen-Yue Chang, Hui-Xia He, Department of Stomatology, First Medical Center of Chinese PLA General Hospital and Medical School of Chinese PLA, Beijing 100853, China
Qiao-Zhen Qin, Xiao-Tong Li, Yue Chen, Hua-Qiang Ruan, Xiao-Xia Jiang, Institute of Basic Medical Sciences, Beijing 100850, China
Jia-Jing Wang, Strategic Support Force Characteristic Medical Center of Chinese PLA, Beijing 100101, China
Yan-Nv Qu, Department of Geriatrics, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
Co-corresponding authors: Xiao-Xia Jiang and Hui-Xia He.
Author contributions: Jiang XX and He HX contribute equally to this study as co-corresponding authors; Jiang XX was responsible for supervision, writing - review & editing, funding acquisition, resources; He HX was responsible for supervision, resources; Chang WY was responsible for conceptualization, investigation, writing - original draft, methodology, formal analysis; Qin QZ was responsible for data curation, software; Li XT was responsible for investigation, methodology; Wang JJ was responsible for validation; Chen Y was responsible for project administration; Ruan HQ was responsible for writing - review & editing; Qu YN was responsible for funding acquisition.
Supported by Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515012394.
Institutional animal care and use committee statement: All animal experiments were conducted according to the Guide for the Care and Use of Laboratory Animals by the Administrative Panel on Laboratory Animal Care at the Institute of Basic Medical Sciences (Beijing, China, No. IACUC-DWZX-2024-530).
Conflict-of-interest statement: The author(s) report no conflict of interest in this work.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Xia He, Department of Stomatology, First Medical Center of Chinese PLA General Hospital and Medical School of Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. hehuixia@301hospital.com.cn
Received: January 2, 2025 Revised: March 11, 2025 Accepted: April 21, 2025 Published online: June 19, 2025 Processing time: 147 Days and 7.2 Hours
Abstract
BACKGROUND
Hypobaric hypoxia exposure (HHE) often causes neuropsychiatric disorders. Due to its complex mechanism, efficient strategies for alleviating HHE-induced anxiety- and depression-like behaviors remain limited.
AIM
To characterize alterations in the oral and gut microbiota following HHE and to explore a potential microbiota-based intervention to mitigate associated psychiatric symptoms.
METHODS
C57BL/6J mice were exposed to simulated high-altitude hypoxia (5000 m) for 1, 3, 5, or 7 days. Behavioral assessments, including the open field test, elevated plus maze, and forced swim test, were conducted to evaluate anxiety- and depression-like behaviors. Oral and fecal microbiota were analyzed using 16S rRNA sequencing to assess changes in microbial composition and diversity. Immunofluorescence staining was performed to examine c-Fos expression in brain nuclei. A probiotic formulation containing Lactobacillus rhamnosus (L. rhamnosus) DSM17648, Lactobacillus acidophilus DDS-1, and L. rhamnosus UALR-06 was administered to mice subjected to one day of HHE (HH1) to evaluate its therapeutic efficacy.
RESULTS
Behavioral tests revealed that HHE caused anxiety- and depression-like behaviors, which were most pronounced after 1 day of exposure. The IF data revealed significantly increased expression of c-Fos in various brain nuclei after HHE, including the anterior cingulate cortex, paraventricular thalamic nucleus, lateral habenula nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, and periaqueductal gray. The 16S rRNA sequencing results demonstrated a sharp decline in the abundance of Lactobacillus in the oral microbiota of mice exposed to HH1 and a marked decrease in the abundance of Lactobacillus and Bifidobacterium in the fecal microbiota of mice exposed to three days of HHE. Finally, oral administration and gavage of Lactobacillus significantly alleviated anxiety- and depression-like behaviors in HH1 mice.
CONCLUSION
HHE caused significant variations in the oral and fecal microbiota of mice. Lactobacillus supplementation alleviated anxiety- and depression-like behaviors in mice. Improving oral flora may relieve HHE-induced psychiatric disorders.
Core Tip: The effects of hypobaric hypoxia (HH) exposure (HHE) on anxiety- and depression-like behaviors in mice were analyzed. HHE for one day activated several brain nuclei, including the anterior cingulate cortex, paraventricular thalamic nucleus, lateral habenula, paraventricular hypothalamic nucleus, lateral hypothalamus, and anterior periaqueductal gray. A significant decrease in Lactobacillus abundance was found in the oral microbiota following one day of HH. Both oral application and gavage administration of a Lactobacillus complex effectively alleviated anxiety- and depression-like behaviors in mice subjected to one day of HH.
