Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Microbiota Research Center and Emerging Viral Infections Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Int J Mol Sci. 2022 Oct 28;23(21):13070. doi: 10.3390/ijms232113070.
Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, MTS01 could be developed as a next-generation probiotic for ameliorating ASD.
自闭症谱系障碍(ASD)的特征是认知灵活性和社交缺陷。益生菌已被证明在缓解 ASD 的严重程度方面具有广阔的应用前景。然而,目前尚无有效的益生菌可供临床使用。因此,鉴定新的益生菌菌株以改善 ASD 至关重要。本研究使用基于母体免疫激活(MIA)的 ASD 样小鼠模型,对雌性小鼠进行了益生菌干预策略的研究。此前已证明肠道共生微生物 MTS01 对慢性炎症相关疾病具有多种有益作用,本研究对其进行了评估。产前脂多糖(LPS)暴露可诱导结肠出现肠道渗漏相关的炎症表型,增加血清中 LPS 的活性,并诱导后代小鼠出现自闭症样行为。相比之下,MTS01 治疗可显著减轻肠道和全身炎症,并改善疾病的发展。MIA 后代的转录组分析表明,在肠道中,MTS01 增强了神经肽相关信号通路,抑制了异常的细胞增殖和炎症反应。在海马体中,MTS01 增加了核糖体/线粒体和抗氧化活性,减少了谷氨酸受体信号。总之,MTS01 对 MIA 后代的 ASD 相关行为具有显著的改善作用。因此,MTS01 可被开发为一种新型益生菌,用于改善 ASD。