Effects of Corona and Astrovirus infections on the gut microbiomes of bats: the Hipposideros species complex as a model for virus-induced increase of pathogenic bacteria in highly gregarious mammals

脊椎动物的肠道微生物群不仅具有代谢功能，也是免疫防御机制的重要驱动因素。为了发挥这些作用，肠道微生物群落需要一定的稳定性和一致性。肠道病毒可以扰乱微生物群落的平衡，这可能导致继发性感染，并转向更多的致病微生物物种。如果这种情况发生在已知病原体宿主物种中，则可能出现较高的人畜共患风险。蝙蝠是大量人畜共患病原体的进化起源和宿主。其中包括星状病毒（AstV），它是世界范围内导致儿童感染性腹泻的主要原因，以及不同的胃肠道冠状病毒（CoV），它们是最近引起人类高致病性SARS和中东呼吸综合征流行的病毒的祖先。蝙蝠也是人畜共患细菌的宿主，尽管这些还没有得到充分的研究。我们在此提出采用四种生态相似物种的蝙蝠模型，与人类一样，它们以大群体和密度生活，以研究冠状病毒和AstV感染在肠道中引起的微生物组变化。我们的目标是确定病毒-微生物组相互作用及其对细菌物种群落和基因功能水平的影响，以便了解在高度群居的哺乳动物中，哪些致病性和潜在的人畜共患病毒诱导的群体范围内的微生物组变化可能出现。来自加纳中部5个独立地点的4种河马的6500多个病毒筛选样本已经从以前由德国政府资助的“德国-非洲传染病学合作项目”项目中获得。与以往研究野生水库物种微生物组变化的研究相比，我们的研究设计提供了难得的机会来控制系统发育和环境变化，这将使我们能够区分环境因素、病毒诱导因素和内在因素。

The gut microbiome of a vertebrate has not only metabolic functions, it is also an important driver of immune defence mechanisms. To fulfil these roles, some stability and consistency within the gut microbial community is required. Enteric viruses can disturb the balance of the microbial communities, which can lead to secondary infections and to shifts towards higher number of pathogenic microbe species. If this happens in known pathogen reservoir species, a higher zoonotic risk may arise. Bats constitute the evolutionary origin and reservoirs of a high number of zoonotic pathogens. Among them are astroviruses (AstV), the worldwide leading cause of infectious diarrhoea in children, and different gastrointestinal coronavirus (CoV) species that constitute the ancestors of the viruses that recently caused highly pathogenic SARS and MERS epidemics in humans. Bats are also hosts of zoonotic bacteria although these are understudied. We here propose employing a bat model of four ecologically similar species that – like humans – live in large groups and densities to investigate the microbiome changes induced by CoVs and AstV infections in the gut. Our aim is to identity virus-microbiome interactions and their consequences on the bacterial species community and gene function level in order to understand which pathogenetic and potentially zoonotic virus-induced population-wide microbiome changes may arise in highly gregarious mammals. More than 6500 virus-screened samples from four Hipposideros species from five independent locations in central Ghana are already available from the previous DFG-funded program ‘German-African Cooperation Projects in Infectology’. In contrast to previous studies investigating microbiome changes in wild reservoir species, our study design provides the rare opportunity to control for phylogenetic and environmental variation which will enable us to discriminate between environmental, virus-induced and intrinsic factors.