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选择性益生菌治疗对自闭症BTBR小鼠模型中的微生物群-肠-脑轴具有正向调节作用。

Selective Probiotic Treatment Positively Modulates the Microbiota-Gut-Brain Axis in the BTBR Mouse Model of Autism.

作者信息

Pochakom Angela, Mu Chunlong, Rho Jong M, Tompkins Thomas A, Mayengbam Shyamchand, Shearer Jane

机构信息

Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Departments of Neurosciences, Pediatrics and Pharmacology, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

出版信息

Brain Sci. 2022 Jun 14;12(6):781. doi: 10.3390/brainsci12060781.

Abstract

Recent studies have shown promise for the use of probiotics in modulating behaviour through the microbiota-gut-brain axis. In the present study, we assessed the impact of two probiotic strains in mitigating autism-related symptomology in the BTBR /J mouse model of autism spectrum disorder (ASD). Male juvenile BTBR mice were randomized into: (1) control, (2) probiotic (1 × 10 CFU/mL HA-114), and (3) probiotic groups (1 × 10 CFU/mL HA-118) (n = 18-21/group), receiving treatments in drinking water for 4 weeks. Gut microbiota profiling by 16S rRNA showed , but not supplementation, to increase microbial richness and phylogenetic diversity, with a rise in potential anti-inflammatory and butyrate-producing taxa. Assessing serum and brain metabolites, and supplementation produced distinct metabolic profiles, with treatment elevating concentrations of potentially beneficial neuroactive compounds, such as 5-aminovaleric acid and choline. As mitochondrial dysfunction is often observed in ASD, we assessed mitochondrial oxygen consumption rates in the prefrontal cortex and hippocampus. No differences were observed for either treatment. Both and treatment reduced behavioural deficits in social novelty preference. However, no changes in hyperactivity, repetitive behaviour, and sociability were observed. Results show to impart positive changes along the microbiota-gut-brain axis, exhibiting beneficial effects on selected behaviour, gut microbial diversity, and metabolism in BTBR mice.

摘要

最近的研究表明,益生菌有望通过微生物群-肠-脑轴调节行为。在本研究中,我们评估了两种益生菌菌株对减轻自闭症谱系障碍(ASD)的BTBR /J小鼠模型中自闭症相关症状的影响。雄性幼年BTBR小鼠被随机分为:(1)对照组,(2)益生菌组(1×10 CFU/mL HA-114),和(3)益生菌组(1×10 CFU/mL HA-118)(每组n = 18-21),通过饮用水接受治疗4周。通过16S rRNA进行的肠道微生物群分析显示,补充[未提及的物质]可增加微生物丰富度和系统发育多样性,但补充[未提及的物质]则不然,同时潜在的抗炎和产生丁酸盐的分类群有所增加。在评估血清和脑代谢物时,补充[未提及的物质]和[未提及的物质]产生了不同的代谢谱,补充[未提及的物质]治疗可提高潜在有益神经活性化合物的浓度,如5-氨基戊酸和胆碱。由于在ASD中经常观察到线粒体功能障碍,我们评估了前额叶皮质和海马体中的线粒体氧消耗率。两种治疗均未观察到差异。补充[未提及的物质]和[未提及的物质]治疗均减少了社交新奇偏好方面的行为缺陷。然而,在多动、重复行为和社交能力方面未观察到变化。结果表明,[未提及的物质]可沿微生物群-肠-脑轴产生积极变化,对BTBR小鼠的特定行为、肠道微生物多样性和代谢具有有益影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09a1/9220969/b7a837fa5a6e/brainsci-12-00781-g001.jpg

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