Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice

Abstract Plateau environment represents a common terrestrial characterized by multistress conditions including hypobaric hypoxia, low temperature, and intense radiation, yet sustain over 100 million permanent or transient inhabitants. While this extreme environment exerts profound impacts on cerebra...

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Main Authors: Baoxing Gan, Xufei Zhang, Jinge Xin, Lixiao Duan, Ning Sun, Yu Chen, Junqi Zeng, Yueying Lian, Hao Li, Hesong Wang, Xueqin Ni, Hailin Ma
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:AMB Express
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Online Access:https://doi.org/10.1186/s13568-025-01898-2
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author Baoxing Gan
Xufei Zhang
Jinge Xin
Lixiao Duan
Ning Sun
Yu Chen
Junqi Zeng
Yueying Lian
Hao Li
Hesong Wang
Xueqin Ni
Hailin Ma
author_facet Baoxing Gan
Xufei Zhang
Jinge Xin
Lixiao Duan
Ning Sun
Yu Chen
Junqi Zeng
Yueying Lian
Hao Li
Hesong Wang
Xueqin Ni
Hailin Ma
author_sort Baoxing Gan
collection DOAJ
description Abstract Plateau environment represents a common terrestrial characterized by multistress conditions including hypobaric hypoxia, low temperature, and intense radiation, yet sustain over 100 million permanent or transient inhabitants. While this extreme environment exerts profound impacts on cerebral architecture and gut microbiota homeostasis, precipitating cognitive deficits and microbiome-derived intestinal pathologies, the mechanistic interplay between plateau environment adaptation and microbial dynamics remains contentious. Here, we employ a microbiota-gut-brain axis framework to investigate whether probiotic intervention can ameliorate hippocampal impairments induced by simulated plateau environment exposure (3500–4000 m) in mice. Through simulated plateau environment exposure experiments, we revealed that extreme high-altitude conditions induced hippocampal memory dysfunction in mice, exacerbated oxidative stress damage in hippocampal tissues, and altered synaptic plasticity-related biomarkers including CREB transcription factor, BDNF protein levels, and electrophysiological power spectra. Administration of HL79 alleviated these burdens, including memory dysfunction and tissue damage, though complete reversal was not achieved. Combined hippocampal transcriptomic analyses suggested that HL79’s beneficial effects primarily involved modulation of lipid-related gene expression in the hippocampus, consistent with prior reports of plateau environmental impacts on gene expression. Serum metabolomic results further reinforced this inference that differential metabolites regulated by HL79 are mainly enriched in bile secretion, taurine and hypotaurine metabolism, linoleic acid metabolism, and PPAR signaling pathways, though the precise regulatory mechanisms require further elucidation. This research provides a novel microbiota-gut-brain axis-based regulatory strategy for adaptation to extreme plateau environments and offers new evidence for understanding the relationship between gut microbiota and plateau environment adaptation at high elevations.
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spelling doaj-art-82b124fbb96845fe9bdfcbc3f6320d1e2025-08-20T03:47:16ZengSpringerOpenAMB Express2191-08552025-06-0115111710.1186/s13568-025-01898-2Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in miceBaoxing Gan0Xufei Zhang1Jinge Xin2Lixiao Duan3Ning Sun4Yu Chen5Junqi Zeng6Yueying Lian7Hao Li8Hesong Wang9Xueqin Ni10Hailin Ma11Animal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural UniversityPlateau Brain Science Research Center, Tibet UniversityDepartment of Gastroenterology, Baiyun District Peoples Hospital of GuangzhouAnimal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural UniversityAnimal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural UniversityAnimal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural UniversitySchool of Basic Medical Sciences, Southern Medical UniversitySchool of Public Health, Southern Medical UniversityPlateau Brain Science Research Center, Tibet UniversityDepartment of Rehabilitation Medicine, Baiyun District Peoples Hospital of GuangzhouAnimal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural UniversityPlateau Brain Science Research Center, Tibet UniversityAbstract Plateau environment represents a common terrestrial characterized by multistress conditions including hypobaric hypoxia, low temperature, and intense radiation, yet sustain over 100 million permanent or transient inhabitants. While this extreme environment exerts profound impacts on cerebral architecture and gut microbiota homeostasis, precipitating cognitive deficits and microbiome-derived intestinal pathologies, the mechanistic interplay between plateau environment adaptation and microbial dynamics remains contentious. Here, we employ a microbiota-gut-brain axis framework to investigate whether probiotic intervention can ameliorate hippocampal impairments induced by simulated plateau environment exposure (3500–4000 m) in mice. Through simulated plateau environment exposure experiments, we revealed that extreme high-altitude conditions induced hippocampal memory dysfunction in mice, exacerbated oxidative stress damage in hippocampal tissues, and altered synaptic plasticity-related biomarkers including CREB transcription factor, BDNF protein levels, and electrophysiological power spectra. Administration of HL79 alleviated these burdens, including memory dysfunction and tissue damage, though complete reversal was not achieved. Combined hippocampal transcriptomic analyses suggested that HL79’s beneficial effects primarily involved modulation of lipid-related gene expression in the hippocampus, consistent with prior reports of plateau environmental impacts on gene expression. Serum metabolomic results further reinforced this inference that differential metabolites regulated by HL79 are mainly enriched in bile secretion, taurine and hypotaurine metabolism, linoleic acid metabolism, and PPAR signaling pathways, though the precise regulatory mechanisms require further elucidation. This research provides a novel microbiota-gut-brain axis-based regulatory strategy for adaptation to extreme plateau environments and offers new evidence for understanding the relationship between gut microbiota and plateau environment adaptation at high elevations.https://doi.org/10.1186/s13568-025-01898-2Plateau environmentMicrobiota-gut-brain axisProbioticsSpatial memory dysfunction
spellingShingle Baoxing Gan
Xufei Zhang
Jinge Xin
Lixiao Duan
Ning Sun
Yu Chen
Junqi Zeng
Yueying Lian
Hao Li
Hesong Wang
Xueqin Ni
Hailin Ma
Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
AMB Express
Plateau environment
Microbiota-gut-brain axis
Probiotics
Spatial memory dysfunction
title Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
title_full Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
title_fullStr Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
title_full_unstemmed Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
title_short Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice
title_sort lactobacillus johnsonii hl79 mitigate plateau environment induced hippocampal dysfunction in mice
topic Plateau environment
Microbiota-gut-brain axis
Probiotics
Spatial memory dysfunction
url https://doi.org/10.1186/s13568-025-01898-2
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