嗜黏蛋白阿克曼菌及其释放的外膜囊泡缓解应激结直肠癌小鼠的焦虑与抑郁情绪  

Akkermansia muciniphila and its released outer membrane vesicles alleviate anxiety and depressive behaviors in stress-induced colorectal cancer mice

作　　者：靳顺康 鲁艳杰 陈彤彤 张鑫宇 李杨 李玉红 JIN Shunkang;LU Yanjie;CHEN Tongtong;ZHANG Xinyu;LI Yang;LI Yuhong(Cancer Research Laboratory,Chengde Medical College,Chengde,Hebei 067000,China;不详)

机构地区：[1]承德医学院基础医学院肿瘤研究室,河北承德067000 [2]军事科学院军事医学研究院辐射医学研究所

出　　处：《中国微生态学杂志》2025年第2期182-188,共7页Chinese Journal of Microecology

基　　金：河北省自然科学基金面上项目(H2024406009);中央引导地方科技发展资金项目(236Z7701G);承德医学院交叉探索科研专项重点项目(KY202402)。

摘　　要：目的探究嗜黏蛋白阿克曼菌(A.muciniphila)及其释放的外膜囊泡(OMV)对应激结直肠癌小鼠模型焦虑和抑郁情绪的影响。方法将70只C57BL/6J小鼠分为Control组、CAC组、A.muciniphila组、CS组、CSAM组、OMV组和CSOMV组,每组10只。采用氧化偶氮甲烷与葡聚糖硫酸钠溶液联合用药建立结肠炎相关结直肠癌模型。小鼠每天随机暴露于1~2种轻度应激刺激,持续14 d建立慢性应激模型。采用A.muciniphila菌液和A.muciniphila OMV悬浮液灌胃干预应激结直肠癌小鼠。采用旷场实验检测小鼠焦虑情绪,采用悬尾实验检测小鼠抑郁情绪。16S rDNA基因测序检测小鼠肠道微生物群落的改变。结果与CS组小鼠相比,A.muciniphila干预后慢性应激结直肠癌小鼠旷场箱内探索总路程(t=4.747,P<0.001)和平均速度(t=4.691,P<0.001)均显著增加。悬尾实验的不动时间(t=2.270,P<0.05)和不动时间百分比(t=2.273,P<0.05)显著减少。与CS组小鼠相比,A.muciniphila OMV干预后慢性应激结直肠癌小鼠旷场箱内探索总路程(t=3.167,P<0.05)和平均速度(t=3.264,P<0.01)均显著增加。悬尾实验中不动时间(t=2.409,P<0.05)和不动时间百分比(t=3.969,P<0.01)显著减少。16S rDNA基因测序表明,与CS组比较,CSOMV组中考拉杆菌属、Colidextribacter、布劳特菌属、Faecalibacterium、罕见小球菌属、嗜胆菌属、Olsenella、Angelakisella和酸硫杆菌属的相对丰度显著增加(P<0.05),Parvibacter相对丰度显著减少(P<0.05)。结论A.muciniphila及其分泌的外膜囊泡能够有效缓解应激结直肠癌小鼠的焦虑和抑郁情绪,并显著改变慢性应激结直肠癌小鼠的肠道菌群。Objective To observe the effects of Akkermansia muciniphila and the outer membrane vesicles(OMVs)its released on anxiety and depression-like behaviors in chronic stress-induced colorectal cancer(CC)mouse model.Methods Seventy C57BL/6J mice were divided into seven groups:Control,CAC,A.muciniphila,CS,CSAM,OMV and CSOMV,with 10 mice per group.A colitis-associated CC model was established using a combination of azoxymethane and dextran sulfate sodium solution.A chronic stress model was established by exposing mice to 1-2 types of mild stress stimuli randomly per day for 14 days.Intervention was carried out by oral administration of A.muciniphila suspension or A.muciniphila OMV suspension.Anxiety-like behavior was assessed using the open field test,and depression-like behavior was evaluated using the tail suspension test.16S rDNA gene sequencing was performed to analyze the changes in gut microbiota.Results Compared with the CS group,A.muciniphila intervention significantly increased the total exploration distance(t=4.747,P<0.001)and average speed(t=4.691,P<0.001)in the open field test,and significantly decreased immobility time(t=2.270,P<0.05)and immobility percentage(t=2.273,P<0.05)in the tail suspension test.A.muciniphila OMV intervention significantly increased the total exploration distance(t=3.167,P<0.05)and average speed(t=3.264,P<0.01)in the open field test,and significantly decreased immobility time(t=2.409,P<0.05)and immobility percentage(t=3.969,P<0.01)in the tail suspension test.16S rDNA gene sequencing revealed that,compared with the CS group,the CSOMV group exhibited a significant increase in the relative abundance of Phascolarctobacterium,Colidextribacter,Blautia,Faecalibacterium,Subdoligranulum,Bilophila,Olsenella,Angelakisella and Acidithiobacillus,while that of Parvibacter was significantly decreased.Conclusion A.muciniphila and its secreted OMVs effectively alleviated anxiety-and depression-like behaviors in chronic stress-induced CC mice,and A.muciniphila OMVs significantly altered the gut microbio

关 键 词：慢性应激 结直肠癌 肠道菌群 嗜黏蛋白阿克曼菌 外膜囊泡 

分 类 号：R749.4[医药卫生—神经病学与精神病学]