TY - JOUR
T1 - Dysbiosis of the oral-gut microbiome axis in a mouse model of depression
AU - Lei, Pu
AU - Tong, Shaonan
AU - Xi, Wenyu
AU - Liu, Yixin
AU - Yu, Jiayue
AU - Yu, Lu
AU - Zhao, Binbin
AU - Jia, Min
AU - Li, Ye
AU - Ma, Xiancang
AU - Wang, Yunpeng
AU - Guo, Yijie
N1 - Publisher Copyright:
Copyright: © 2026 Lei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2026
Y1 - 2026
N2 - This study aimed to characterize the alterations in both oral and gut microbiota in a mouse model of depression and to explore their potential role in the pathogenesis of major depressive disorder (MDD) through the oral-gut-brain axis. A depression model was established in male C57BL/6J mice using chronic social defeat stress (CSDS) paradigm. Depressive phenotypes were confirmed through social interaction, sucrose preference, open field, tail suspension, and forced swim tests. The microbial composition of oral and gut samples was analyzed using 16S rRNA sequencing, with Linear Discriminant Analysis Effect Size (LEfSe) employed to identify differentially abundant taxa and Spearman correlation analysis to examine microbiota-behavior relationships. CSDS successfully induced robust depression-like behaviors, including social avoidance, anhedonia, and behavioral despair. Beta-diversity analysis revealed significant separation in oral microbiota between CSDS and control groups. LEfSe analysis identified distinct microbial signatures: control mice were enriched in oral Streptococcus and gut commensals including Lachnospiraceae, Bacteroides and Oscillospiraceae, whereas CSDS mice showed expansion of oral Muribacter and Rodentibacter and gut Alloprevotella, Helicobacter and Colidextribacter. Correlation analyses demonstrated significant associations between specific microbial patterns and depression-like behaviors, with control-enriched taxa negatively correlating with behavioral deficits. Furthermore, significant cross-habitat microbial correlations were observed between oral and gut differential taxa. Our findings demonstrate that CSDS induces divergent microbial alterations in both oral and gut ecosystems, which are systematically associated with depression-like behaviors. These results provide compelling evidence for the involvement of the oral-gut-brain axis in depression pathophysiology and suggest that modulating these microbial ecosystems may represent a potential therapeutic strategy for MDD.
AB - This study aimed to characterize the alterations in both oral and gut microbiota in a mouse model of depression and to explore their potential role in the pathogenesis of major depressive disorder (MDD) through the oral-gut-brain axis. A depression model was established in male C57BL/6J mice using chronic social defeat stress (CSDS) paradigm. Depressive phenotypes were confirmed through social interaction, sucrose preference, open field, tail suspension, and forced swim tests. The microbial composition of oral and gut samples was analyzed using 16S rRNA sequencing, with Linear Discriminant Analysis Effect Size (LEfSe) employed to identify differentially abundant taxa and Spearman correlation analysis to examine microbiota-behavior relationships. CSDS successfully induced robust depression-like behaviors, including social avoidance, anhedonia, and behavioral despair. Beta-diversity analysis revealed significant separation in oral microbiota between CSDS and control groups. LEfSe analysis identified distinct microbial signatures: control mice were enriched in oral Streptococcus and gut commensals including Lachnospiraceae, Bacteroides and Oscillospiraceae, whereas CSDS mice showed expansion of oral Muribacter and Rodentibacter and gut Alloprevotella, Helicobacter and Colidextribacter. Correlation analyses demonstrated significant associations between specific microbial patterns and depression-like behaviors, with control-enriched taxa negatively correlating with behavioral deficits. Furthermore, significant cross-habitat microbial correlations were observed between oral and gut differential taxa. Our findings demonstrate that CSDS induces divergent microbial alterations in both oral and gut ecosystems, which are systematically associated with depression-like behaviors. These results provide compelling evidence for the involvement of the oral-gut-brain axis in depression pathophysiology and suggest that modulating these microbial ecosystems may represent a potential therapeutic strategy for MDD.
UR - https://www.scopus.com/pages/publications/105047061567
U2 - 10.1371/journal.pone.0355302
DO - 10.1371/journal.pone.0355302
M3 - 文章
C2 - 42579664
AN - SCOPUS:105047061567
SN - 1932-6203
VL - 21
SP - e0355302
JO - PLoS ONE
JF - PLoS ONE
IS - 8
ER -