The gut-to-lung axis appears to be significant during respiratory viral infection. Researchers put the hypothesis that disrupted gut homeostasis might be linked to early disease symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To answer this question, the Syrian hamster was used as a model. The research revealed that this model mimics several human lung disease characteristics. It was discovered that SARS-CoV-2 infection is associated with mild intestinal inflammation, a relative change in intestinal barrier function, liver inflammation, as well as altered lipid metabolism. An increase in harmful bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae, as well as an alteration in the gut microbiota composition throughout infection, was observed. Various members in the Ruminococcaceae and Lachnospiraceae families, along with the bacteria which are known to generate fermentative metabolites such as short-chain fatty acids (SCFAs), had a decreased proportion compared to non-infected controls. The infection resulted in a rapid reduction in systemic SCFA levels. The study showed no impact of SCFA supplementation on clinical or inflammatory variables during infection. Finally, researchers found that there was a significant correlation between certain gut microbiota taxa and SARS-CoV-2 infection severity. The study advances the understanding of the COVID-19 pathogenesis by revealing that changes in the gut microbiota are associated with disease severity, suggesting that this experimental hamster model may be useful for developing interventional, pro-inflammatory, therapies to treat COVID-19.