胃肠道(GI)感染与SARS-CoV-2引起的COVID-19发病机制有关。然而,GI微生物群与SARS-CoV-2Proto及其新出现的变种的独特致病性之间的相关性尚不清楚。在这项研究中,我们的目的是确定胃肠道微生物群是否影响COVID-19的发病机制,以及SARS-CoV-2Proto及其变体之间的作用是否不同。我们对组织病理学进行了综合分析,微生物,和感染SARS-CoV-2原蛋白或其变体的恒河猴胃肠道片段的转录组学。根据胃肠道的病理损伤程度和微生物群分布,SARS-CoV-2菌株中的五个被分为两个不同的簇,即,阿尔法簇,Beta和Delta(ABD),以及Proto和Omicron(PO)。值得注意的是,ABD中潜在致病微生物的丰度增加,但在PO感染的恒河猴中没有增加。具体来说,在ABD病毒感染的动物中UCG-002、UCG-005和密螺旋体的高丰度与白细胞介素呈正相关,整合素,和抗病毒基因。总的来说,这项研究表明,感染引起的胃肠道微生物群和代谢产物的改变可以增加感染动物的炎症或病理损伤的全身负担,尤其是那些感染了ABD病毒的人。不同的GI微生物群和代谢物谱可能是PO和ABD病毒感染动物的不同病理表型的原因。这些发现提高了我们对胃肠道微生物在SARS-CoV-2感染中的作用的理解,并为精确预防提供了重要信息。control,和COVID-19的治疗。
Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.