APC Microbiome Institute, University College Cork, Cork, Ireland.
APC Microbiome Institute, University College Cork, Cork, Ireland; School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland.
EBioMedicine. 2017 Oct;24:166-178. doi: 10.1016/j.ebiom.2017.09.020. Epub 2017 Sep 21.
Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR TItpr3/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut - namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.
自闭症谱系障碍（ASD）是全球最常见的神经发育障碍之一。人们越来越意识到，ASD 与胃肠道不适和肠道微生物群改变高度共病，宿主-微生物群相互作用可能导致疾病症状。然而，自闭症中肠道-大脑轴信号的知识匮乏，阻碍了基于微生物组的精准治疗在 ASD 中的发展。为此，我们在 ASD 的 BTBR TItpr3/J 小鼠模型中探索了肠道微生物群、肠道生理学和社会行为之间的相互作用。在这里，我们表明 BTBR 肠道中某些特定细菌类群的相对丰度减少，即胆汁代谢双歧杆菌和布劳特氏菌属，与肠道中胆汁酸和色氨酸代谢缺陷、明显的胃肠道功能障碍以及 BTBR 小鼠的社交互动受损有关。这些数据共同支持了靶向肠道微生物群来逆转 ASD 中胃肠道和行为症状的概念，并为这一努力提供了具体的可行目标。
