Cell:宿主基因和肠道菌群如何合力造成自闭症行为?
  • 利用敲除Cntnap2基因的自闭症小鼠模型,研究宿主基因与肠道菌群对行为的影响;
  • 意外发现:多动由宿主基因主导,社交障碍则由肠道菌群介导;
  • 补充罗伊氏乳杆菌ATCC 6475或代谢产物四氢生物蝶呤(BH4),可改善社交障碍而非多动;
  • 阻断BH4合成通路,补充罗伊氏乳杆菌无法改善小鼠社交障碍;
  • 补充罗伊氏乳杆菌和BH4可促进小鼠脑部社交奖赏机制介导的突触传递。
主编推荐语
元气少女617(ꈍᴗꈍ)
过去,我们通常认为,影响大脑发育和功能的基因发生突变是造成行为异常的主要原因。然而,近期的微生物组研究揭示了肠-脑轴的存在,表明微生物组也可能会调控影响宿主行为。但是我们尚不清楚宿主基因和微生物组是如何共同调控复杂行为的。Mauro Costa-Mattioli团队发表的这篇研究通过共同饲养、菌群移植等多种手段证明了在自闭症小鼠模型中,社会行为由肠道菌群调控,而宿主基因影响小鼠多动表现。此外,基于前期的研究(查看文章),作者发现罗伊氏乳杆菌可以改善小鼠的社会行为缺陷,并揭示了其背后的新机制,即罗伊氏乳杆菌-四氢生物蝶呤(BH4)-宿主社交行为轴。该文提示我们未来针对自闭症等神经疾病的治疗方案应综合靶向大脑和菌群,推荐仔细阅读原文。
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Cell [IF:38.637]

Dissecting the contribution of host genetics and the microbiome in complex behaviors

剖析宿主遗传学和微生物组在复杂行为中的贡献

10.1016/j.cell.2021.02.009

03-10, Article

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The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2 −/− model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2 −/− mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Interestingly, specific microbial intervention selectively rescued the social deficits in Cntnap2 −/− mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. Our findings that behavioral abnormalities could have distinct origins (host genetic versus microbial) may change the way we think about neurological disorders and how to treat them.

First Authors:
Shelly A Buffington,Sean W Dooling

Correspondence Authors:
Mauro Costa-Mattioli

All Authors:
Shelly A Buffington,Sean W Dooling,Martina Sgritta,Cecilia Noecker,Oscar D Murillo,Q Daniela F Felice,Peter J Turnbaugh,Mauro Costa-Mattioli

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Cell重磅:用益生菌治疗大脑疾病,改善社交行为!

2021-03-11

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