南方医科大学学报2025，Vol.45Issue(3)：554-565,12.DOI:10.12122/j.issn.1673-4254.2025.03.13
Akkermansia muciniphila改善gp120转基因小鼠的肠-脑相互作用障碍
Akkermansia muciniphila gavage improves gut-brain interaction disorders in gp120 transgenic mice
摘要
Abstract
Objective To explore the effect of A.muciniphila gavage on intestinal microbiota and gut-brain interaction disorders(DGBIs)in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder(HAND).Methods Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-,9-,and 12-month-old wild-type(WT)mice and gp120tg transgenic mice.The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage(2×108 CFU/mouse)for 6 weeks.After the treatment,immunohistochemistry,ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins,MBP and IL-1β,eosinophil infiltration,serum lipopolysaccharide(LPS)levels,and colonic expressions of occludin,ZO-1,IL-10,TNF-α and INF-γ mRNA.Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.Results Compared with WT mice,the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus,increased serum LPS levels and decreased colonic expression of glycosylated mucin.A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight.The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β,INF-γ and IL-1β levels and obviously lowered IL-10 level;all these changes were significantly mitigated by A.muciniphila gavage,which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.Conclusion The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice.The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes,and A.muciniphila gavage can reduce intestinal barrier injury,colonic inflammation and eosinophil activation,cognitive impairment and brain neuron injury in these mice.关键词
gp120/肠道菌群/肠-脑相互作用障碍/嗜酸性粒细胞/神经认知功能损伤/Akkermansia muciniphilaKey words
gp120/gut microbiota/gut-brain interaction disorders/eosinophils/neurocognitive impairment/Akkermansia muciniphila引用本文复制引用
罗嘉纯,Batzaya Sodnomjamts,高雪锋,陈晶宇,余政颖,熊莎莎,曹虹..Akkermansia muciniphila改善gp120转基因小鼠的肠-脑相互作用障碍[J].南方医科大学学报,2025,45(3):554-565,12.基金项目
国家自然科学基金(82172259) （82172259）
广东省自然科学基金(2024A1515010606) Supported by Natural Science Foundation of China(82172259). （2024A1515010606）
