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

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2025-04-20 DOI:10.12122/j.issn.1673-4254.2025.04.04

Yang Yang, Kai Wang, Jianxiu Liu, Zhimo Zhou, Wen Jia, Simou Wu, Jinxing Li, Fang He, Ruyue Cheng

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Abstract

Objectives: 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 enhanced α diversity 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.

Conclusions: 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.

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[早期两歧双歧杆菌BD-1干预可减轻注意缺陷多动障碍幼年雌性大鼠的多动症]。

目的：探讨两歧双歧杆菌BD-1 （B. bifidum BD-1）早期生命干预对注意缺陷多动障碍（ADHD）雌性小鼠模型多动症的影响，并探讨其机制。方法：8只新生雌性wista - kyoto （WKY）大鼠和6只自发性高血压大鼠（SHRs）灌胃生理盐水，6只自发性高血压大鼠灌胃双歧杆菌BD-1 (109 CFU)，连续3周。7周龄时对大鼠进行野外试验，断奶（3周龄）和7周龄时采集粪便样本进行16S rRNA测序。采用免疫荧光染色检测纹状体中多巴胺转运体（DAT）和酪氨酸羟化酶（Th）水平以及前额皮质活化的小胶质细胞。用流式细胞术分析肠系膜淋巴结、脾脏和血液中的Treg细胞。结果：与WKY大鼠相比，裸地试验中SHRs的移动距离明显增加，两歧双歧杆菌BD-1干预显著减弱了这种行为。shr大鼠纹状体中DAT和Th的表达明显低于WKY大鼠，而两歧双歧杆菌BD-1处理明显提高了shr大鼠纹状体中Th的表达。两歧双歧杆菌BD-1干预显著降低了SHRs脾脏中活化的小胶质细胞数量，增加了Treg细胞计数。该处理还增强了SHRs肠道菌群α多样性，降低了厚壁菌门/拟杆菌门比例，增强了Muribaculaceae的活性，抑制了Clostridia_UCG-014的增殖。结论：早期生命干预双歧杆菌BD-1可通过调节肠道菌群和外周免疫反应、抑制神经炎症和改善多巴胺能系统功能来缓解女性SHRs的多动症。这些发现为ADHD的早期预防策略提供了证据，并支持了精神药物的开发和应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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