Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2

Abstract

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS2) affected the geriatric population. Among research models, Golden Syrian hamsters (GSH) are one of the most representative to study SARS2 pathogenesis and host responses. However, animal studies that recapitulate the effects of SARS2 in the human geriatric population are lacking. To address this gap, we inoculated 14 months old GSH with a prototypic ancestral strain of SARS2 and studied the effects on virus pathogenesis, virus shedding, and respiratory and gastrointestinal microbiome changes. SARS2 infection led to high vRNA loads in the nasal turbinates (NT), lungs, and trachea as well as higher pulmonary lesions scores later in infection. Dysbiosis throughout SARS2 disease progression was observed in the pulmonary microbial dynamics with the enrichment of opportunistic pathogens (Haemophilus, Fusobacterium, Streptococcus, Campylobacter, and Johnsonella) and microbes associated with inflammation (Prevotella). Changes in the gut microbial community also reflected an increase in multiple genera previously associated with intestinal inflammation and disease (Helicobacter, Mucispirillum, Streptococcus, unclassified Erysipelotrichaceae, and Spirochaetaceae). Influenza A virus (FLUAV) pre-exposure resulted in slightly more pronounced pathology in the NT and lungs early on (3 dpc), and more notable changes in lungs compared to the gut microbiome dynamics. Similarities among aged GSH and the microbiome in critically ill COVID-19 patients, particularly in the lower respiratory tract, suggest that GSHs are a representative model to investigate microbial changes during SARS2 infection. The relationship between the residential microbiome and other confounding factors, such as SARS2 infection, in a widely used animal model, contributes to a better understanding of the complexities associated with the host responses during viral infections.

Exploring gut–lung axis crosstalk in SARS‐CoV‐2 infection: Insights from a hACE2 mouse model

“…In this context, the establishment of animal experimental models capable of faithfully replicating gut microbiota alterations in response to COVID‐19 is of paramount significance. While various models have been explored, including K18‐hACE2 transgenic mice, hamsters, and nonhuman primates, none have reported the detection of infectious viruses within the gut, 17–21 which is believed to directly influence the gut microbiota 22,23 . In our prior research, we successfully established a novel humanized ACE2 knock‐in (hACE2‐KI) mouse model capable of recapitulating both pulmonary and intestinal SARS‐CoV‐2 infection 24 .…”

“…While various models have been explored, including K18-hACE2 transgenic mice, hamsters, and nonhuman primates, none have reported the detection of infectious viruses within the gut, [17][18][19][20][21] which is believed to directly influence the gut microbiota. 22,23 In our prior research, we successfully established a novel humanized ACE2 knock-in (hACE2-KI) mouse model capable of recapitulating both pulmonary and intestinal SARS-CoV-2 infection. 24 Consequently, we leveraged this model in the current study to investigate the responses of the gut microbiota to SARS-CoV-2 infection, recognizing the susceptibility of gut microbiota to the virus.…”