生命早期两歧双歧杆菌BD-1干预可缓解注意缺陷多动障碍雌性大鼠幼年期的多动行为  

Early life Bifidobacterium bifidum BD-1 intervention alleviates hyperactivity of juvenile female rats with attention deficit hyperactivity disorder

作　　者：杨洋 王凯 柳鉴修 周志谟 贾雯 吴思谋 李金星 何方 程如越 YANG Yang;WANG Kai;LIU Jianxiu;ZHOU Zhimo;JIA Wen;WU Simou;LI Jinxing;HE Fang;CHENG Ruyue(West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西公共卫生学院//华西第四医院,四川成都610041

出　　处：《南方医科大学学报》2025年第4期702-710,共9页Journal of Southern Medical University

基　　金：国家自然科学基金青年科学基金(82204037);中国博士后科学基金(2022M712228);四川大学专职博士后科研基金(2022SCU12026)。

摘　　要：目的研究生命早期两歧双歧杆菌BD-1干预对幼年期注意缺陷多动障碍(ADHD)雌性自发性高血压大鼠(SHR)模型的影响及机制。方法对雌性新生Wistar-Kyoto(WKY)大鼠(空白对照组,n=8)和SHR(模型组,n=6)灌胃生理盐水,同时对雌性新生SHR灌胃BD-1(109 CFU/d,实验组,n=6)。3周龄时停止灌胃并采集粪便,7周龄时进行旷场实验并采集粪便,随后处死大鼠。对肠道菌群进行16S rRNA测序,对纹状体多巴胺转运体和酪氨酸羟化酶、前额皮质活化小胶质细胞进行免疫荧光染色,流式细胞术检测肠系膜淋巴结、脾脏和血液中Treg细胞数量。结果SHR在旷场中的运动距离高于WKY(P<0.0001),BD-1干预降低了SHR的运动距离(P<0.01)。SHR纹状体中多巴胺转运体(P<0.05)和酪氨酸羟化酶(P<0.05)表达低于WKY,BD-1干预增加了SHR酪氨酸羟化酶的表达(P<0.05)。BD-1干预减少了SHR前额皮质活化小胶质细胞数(P<0.01)、增加了SHR脾脏中Treg细胞数(P<0.01)。BD-1干预增加了SHR肠道菌群α多样性、降低厚壁菌门/拟杆菌门比值,促进Muribaculaceae生长、抑制Clostridia_UCG-014生长。结论生命早期两歧双歧杆菌BD-1干预通过调节肠道菌群、调节外周免疫、抑制神经炎症、改善多巴胺能神经系统功能,从而缓解宿主后期多动行为,为ADHD的早期预防和精神益生菌的开发应用提供科学依据。Objective To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1(B.bifidum BD-1)on hyperactivity in a female mouse model of attention deficit hyperactivity disorder(ADHD)and explore the underlying mechanisms.Methods Eight newborn female Wistar-Kyoto(WKY)rats and 6 spontaneous hypertensive rats(SHRs)were gavaged with saline and another 6 SHRs were gavaged with B.bifidum BD-1(109 CFU)daily for 3 weeks.Open field test of the rats was conducted at 7 weeks,and fecal samples were collected at weaning(3 weeks)and at 7 weeks for 16S rRNA sequencing.Immunofluorescent staining was used to detect dopamine transporter(DAT)and tyrosine hydroxylase(Th)levels in the striatum and activated microglia in the prefrontal cortex.Treg cells in the mesenteric lymph nodes,spleen and blood were analyzed using flow cytometry.Results The SHRs traveled a significantly greater distance in open fields test than WKY rats,and this behavior was significantly attenuated by B.bifidum BD-1 intervention.The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats,while B.bifidum BD-1 treatment obviously increased Th levels in the SHRs.B.bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs.The treatment also enhancedαdiversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio,more active Muribaculaceae growth,and suppression of Clostridia_UCG-014 proliferation.Conclusion Early life intervention with B.bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response,suppressing neuroinflammation and improving dopaminergic system function.These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.

关 键 词：注意缺陷多动障碍 两歧双歧杆菌BD-1 微生物-肠-脑轴 生命早期 神经炎症 

分 类 号：R749.94[医药卫生—神经病学与精神病学]