Strickland Britton A, Patel Mira C, Shilts Meghan H, Boone Helen H, Kamali Arash, Zhang Wei, Stylos Daniel, Boukhvalova Marina S, Rosas-Salazar Christian, Yooseph Shibu, Rajagopala Seesandra V, Blanco Jorge C G, Das Suman R
Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Anim Microbiome. 2021 Apr 16;3(1):29. doi: 10.1186/s42523-021-00090-8.
The cotton rat (genus Sigmodon) is an essential small animal model for the study of human infectious disease and viral therapeutic development. However, the impact of the host microbiome on infection outcomes has not been explored in this model, partly due to the lack of a comprehensive characterization of microbial communities across different cotton rat species. Understanding the dynamics of their microbiome could significantly help to better understand its role when modeling viral infections in this animal model.
We examined the bacterial communities of the gut and three external sites (skin, ear, and nose) of two inbred species of cotton rats commonly used in research (S. hispidus and S. fulviventer) by using 16S rRNA gene sequencing, constituting the first comprehensive characterization of the cotton rat microbiome. We showed that S. fulviventer maintained higher alpha diversity and richness than S. hispidus at external sites (skin, ear, nose), but there were no differentially abundant genera. However, S. fulviventer and S. hispidus had distinct fecal microbiomes composed of several significantly differentially abundant genera. Whole metagenomic shotgun sequencing of fecal samples identified species-level differences between S. hispidus and S. fulviventer, as well as different metabolic pathway functions as a result of differential host microbiome contributions. Furthermore, the microbiome composition of the external sites showed significant sex-based differences while fecal communities were not largely different.
Our study shows that host genetic background potentially exerts homeostatic pressures, resulting in distinct microbiomes for two different inbred cotton rat species. Because of the numerous studies that have uncovered strong relationships between host microbiome, viral infection outcomes, and immune responses, our findings represent a strong contribution for understanding the impact of different microbial communities on viral pathogenesis. Furthermore, we provide novel cotton rat microbiome data as a springboard to uncover the full therapeutic potential of the microbiome against viral infections.
棉鼠（棉鼠属）是研究人类传染病和病毒治疗药物开发的重要小型动物模型。然而，宿主微生物群对感染结果的影响在该模型中尚未得到探索，部分原因是缺乏对不同棉鼠物种微生物群落的全面表征。了解其微生物群的动态变化有助于在该动物模型中更好地理解其在病毒感染建模中的作用。
我们通过16S rRNA基因测序检查了常用于研究的两种近交棉鼠物种（刚毛棉鼠和黄腹棉鼠）的肠道以及三个外部部位（皮肤、耳朵和鼻子）的细菌群落，这是对棉鼠微生物群的首次全面表征。我们发现，在外部部位（皮肤、耳朵、鼻子），黄腹棉鼠的α多样性和丰富度高于刚毛棉鼠，但没有差异丰富的属。然而，黄腹棉鼠和刚毛棉鼠有不同的粪便微生物群，由几个显著差异丰富的属组成。粪便样本的全基因组鸟枪法测序确定了刚毛棉鼠和黄腹棉鼠之间的物种水平差异，以及由于宿主微生物群贡献不同而导致的不同代谢途径功能。此外，外部部位的微生物群组成存在显著的性别差异，而粪便群落差异不大。
我们的研究表明，宿主遗传背景可能施加稳态压力，导致两种不同近交棉鼠物种具有不同的微生物群。由于众多研究揭示了宿主微生物群、病毒感染结果和免疫反应之间的密切关系，我们的发现为理解不同微生物群落对病毒发病机制的影响做出了重要贡献。此外，我们提供了新的棉鼠微生物群数据，作为揭示微生物群对病毒感染的全部治疗潜力的跳板。
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