Gut microbiota dysbiosis in adolescent socially isolated mice with cognitive impairment and identification of key pathogenic microbial communities

JING Jinzhou; LI Zelin; LUO Zhengyi; HU Yuying

doi:10.3969/j.issn.1006-5725.2025.19.007

Abstract：Objective To elucidate the role of gut microbiota in cognitive impairment induced by adolescent social isolation(ASI)and identify key pathogenic microbial communities.Methods Sixteen male C57BL/6 mice(postnatal days 21～23)were randomly assigned to a control group(group-housed,4/cage,n=8)or an ASI group(single-housed,1/cage,n=8).After 5 weeks of ASI(5-ASI),fecal samples underwent 16S rRNA sequencing for microbiota analysis.Cognitive behavior was assessed using open field,Y-maze,novel object recognition tests.Correlation analysis integrated microbial abundance with behavioral parameters to screen cognition-associated taxa.Results(1)Behavior:5-ASI mice showed unchanged locomotion(open field)but significantly reduced spontaneous alternation(Y-maze,P<0.01)and lower cognitive index(novel object recognition,P<0.001),confirming spatial and recognition memory deficits.(2)Microbiota:5-ASI mice exhibited decreased α-diversity(P<0.05)and altered β-diversity(P<0.001).LEfSe analysis revealed depleted taxa(e.g.,Prevotellaceae_NK3B31_group,Tyzzerella,Allobaculum,Ruminococcus)and enriched taxa(e.g.,Butyricicoccus,Lachnoclostridium).(3)Correlations:Positive associations with cognitive performance were observed for Prevotellaceae_NK3B31_group,Allobaculum,and Ruminococcus(P<0.05),while Butyricicoccus and Lachnoclostridium showed negative correlations(P<0.05).Conclusion Adolescent social isolation induces spatial/recognition memory impairment and gut microbiota dysbio-sis.Specific microbial alterations(Prevotellaceae_NK3B31_group,Butyricicoccus)correlate with cognitive deficits,providing novel insights into microbiota-mediated mechanisms and potential therapeutic targets.