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已发表论文
青春双歧杆菌 DM8504 通过调节肠道菌群和恢复短链脂肪酸减轻丙戊酸暴露大鼠的自闭症样行为
Authors Liu H, Liu G, Zhang Y , Suo W, Hao Y, Wang Y , Ding H
Received 23 June 2025
Accepted for publication 21 October 2025
Published 7 November 2025 Volume 2025:21 Pages 2449—2463
DOI https://doi.org/10.2147/NDT.S547997
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Taro Kishi
Hui Liu,1,* Gaojie Liu,2,* Yuxuan Zhang,1,* Weicai Suo,1 Yan Hao,2 Yizhong Wang,2,3 Hongfang Ding1
1Department of Pediatrics, Shengli Oil Field Central Hospital, Binzhou Medical University, Dongying, Shandong, People’s Republic of China; 2Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yizhong Wang, Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, People’s Republic of China, Email wangyz@shchildren.com.cn Hongfang Ding, Department of Pediatrics, Shengli Oil Field Central Hospital, Binzhou Medical University, No. 31 Jinan Road, Dongying District, Dongying, Shandong, 257034, People’s Republic of China, Email dinghongfang2019@sohu.com
Objective: Compelling evidence has confirmed that gut microbiota dysbiosis is involved in the development of autism spectrum disorder (ASD). Microbial-based therapies, including probiotics, may provide novel options for ASD management. This study aimed to investigate the alleviative effect of a probiotic strain, Bifidobacterium adolescentis (B. adolescentis) DM8504, on autistic-like behaviors in rats exposed to valproic acid (VPA).
Methods: Male offspring of VPA-exposed pregnant Sprague–Dawley rats treated with B. adolescentis DM8504 were subjected to behavioral tests. Fecal short-chain fatty acids (SCFAs) and microbiota composition were determined by targeted metabolomics and 16S rRNA gene sequencing, respectively. Microbial functional profiles were analyzed using the KEGG and COG pathway analyses.
Results: B. adolescentis DM8504 alleviated autistic-like behaviors in VPA-exposed rats, as evidenced by enhanced locomotor activity, exploratory behavior, sociability, spatial working memory, and depression relief. B. adolescentis DM8504 treatment significantly enhanced the fecal levels of acetic acid, butyric acid, isobutyric acid, propionic acid, and hexanoic acid, and restored the diversity of gut microbiota composition in VPA-exposed rats. Specifically, B. adolescentis DM8504 increased the abundance of gut bacterial species capable of producing SCFAs in VPA-exposed rats, including Bifidobacterium, Faecalibacterium, Eubacterium, and Lachnospiraceae_ NK4A136_group. In addition, microbial functional profile analysis showed that B. adolescentis DM8504 administration reversed the alterations in COG and KEGG pathways induced by VPA exposure.
Conclusion: These findings reveal that B. adolescentis DM8504 alleviates autistic-like behaviors in VPA-exposed rats through restoration of SCFA levels and enrichment of SCFA-producing bacteria, which indicate that well-defined B. adolescentis strains may have potential for the management of children with ASD in the future.
Keywords: ASD, Bifidobacterium adolescentis, probiotic, SCFAs, gut microbiota
1Department of Pediatrics, Shengli Oil Field Central Hospital, Binzhou Medical University, Dongying, Shandong, People’s Republic of China; 2Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yizhong Wang, Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, People’s Republic of China, Email wangyz@shchildren.com.cn Hongfang Ding, Department of Pediatrics, Shengli Oil Field Central Hospital, Binzhou Medical University, No. 31 Jinan Road, Dongying District, Dongying, Shandong, 257034, People’s Republic of China, Email dinghongfang2019@sohu.com
Objective: Compelling evidence has confirmed that gut microbiota dysbiosis is involved in the development of autism spectrum disorder (ASD). Microbial-based therapies, including probiotics, may provide novel options for ASD management. This study aimed to investigate the alleviative effect of a probiotic strain, Bifidobacterium adolescentis (B. adolescentis) DM8504, on autistic-like behaviors in rats exposed to valproic acid (VPA).
Methods: Male offspring of VPA-exposed pregnant Sprague–Dawley rats treated with B. adolescentis DM8504 were subjected to behavioral tests. Fecal short-chain fatty acids (SCFAs) and microbiota composition were determined by targeted metabolomics and 16S rRNA gene sequencing, respectively. Microbial functional profiles were analyzed using the KEGG and COG pathway analyses.
Results: B. adolescentis DM8504 alleviated autistic-like behaviors in VPA-exposed rats, as evidenced by enhanced locomotor activity, exploratory behavior, sociability, spatial working memory, and depression relief. B. adolescentis DM8504 treatment significantly enhanced the fecal levels of acetic acid, butyric acid, isobutyric acid, propionic acid, and hexanoic acid, and restored the diversity of gut microbiota composition in VPA-exposed rats. Specifically, B. adolescentis DM8504 increased the abundance of gut bacterial species capable of producing SCFAs in VPA-exposed rats, including Bifidobacterium, Faecalibacterium, Eubacterium, and Lachnospiraceae_ NK4A136_group. In addition, microbial functional profile analysis showed that B. adolescentis DM8504 administration reversed the alterations in COG and KEGG pathways induced by VPA exposure.
Conclusion: These findings reveal that B. adolescentis DM8504 alleviates autistic-like behaviors in VPA-exposed rats through restoration of SCFA levels and enrichment of SCFA-producing bacteria, which indicate that well-defined B. adolescentis strains may have potential for the management of children with ASD in the future.
Keywords: ASD, Bifidobacterium adolescentis, probiotic, SCFAs, gut microbiota