McAdams Zachary L, Gustafson Kevin L, Russell Amber L, Self Rachel, Petry Amy L, Lever Teresa E, Ericsson Aaron C
Molecular Pathogenesis & Therapeutics Program, University of Missouri, Columbia, MO, USA.
MU Metagenomics Center, University of Missouri, Columbia, MO, USA.
Gut Microbes. 2024 Jan-Dec;16(1):2385524. doi: 10.1080/19490976.2024.2385524. Epub 2024 Aug 6.
Autism spectrum disorders (ASD) are complex human neurodiversities increasing in prevalence within the human population. In search of therapeutics to improve quality-of-life for ASD patients, the gut microbiome (GM) has become a promising target as a growing body of work supports roles for the complex community of microorganisms in influencing host behavior via the gut-brain-axis. However, whether naturally-occurring microbial diversity within the host GM affects these behaviors is often overlooked. Here, we applied a model of population-level differences in the GM to a classic ASD model - the BTBR T Itpr3/J mouse - to assess how complex GMs affect host behavior. Leveraging the naturally occurring differences between supplier-origin GMs, our data demonstrate that differing, complex GMs selectively effect host ASD-related behavior - especially neonatal ultrasonic communication - and reveal a male-specific effect on behavior not typically observed in this strain. We then identified that the body weight of BTBR mice is influenced by the postnatal GM which was potentially mediated by microbiome-dependent effects on energy harvest in the gut. These data provide insight into how variability within the GM affects host behavior and growth, thereby emphasizing the need to incorporate microbial diversity within the host GM as an experimental factor in biomedical research.
自闭症谱系障碍（ASD）是人类复杂的神经多样性，在人群中的患病率不断上升。为了寻找改善ASD患者生活质量的治疗方法，肠道微生物群（GM）已成为一个有前景的靶点，因为越来越多的研究支持微生物复杂群落通过肠-脑轴影响宿主行为。然而，宿主GM中自然存在的微生物多样性是否会影响这些行为常常被忽视。在这里，我们将GM中群体水平差异的模型应用于经典的ASD模型——BTBR T Itpr3/J小鼠，以评估复杂的GM如何影响宿主行为。利用供应商来源的GM之间自然存在的差异，我们的数据表明，不同的复杂GM选择性地影响宿主与ASD相关的行为——尤其是新生儿超声波交流——并揭示了对该品系通常未观察到的行为的雄性特异性影响。然后我们发现，BTBR小鼠的体重受出生后GM的影响，这可能是由微生物群对肠道能量获取的依赖性作用介导的。这些数据为GM内的变异性如何影响宿主行为和生长提供了见解，从而强调在生物医学研究中需要将宿主GM内的微生物多样性作为一个实验因素。
