Butyrate Protects against SARS-CoV-2-induced Tissue Damage in Golden Hamsters

ABSTRACT Butyrate, produced by gut microbe during dietary fiber fermentation, plays anti-inflammatory and antioxidant effects in chronic inflammation diseases, yet it remains to be explored whether butyrate has protective effects against viral infections. Here, we demonstrated that butyrate alleviated tissue injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected golden hamsters with supplementation of butyrate before and during the infection. Butyrate-treated hamsters showed augmentation of type I interferon (IFN) response and activation of endothelial cells without exaggerated inflammation. In addition, butyrate regulated redox homeostasis by enhancing the activity of superoxide dismutase (SOD) to inhibit excessive apoptotic cell death. Therefore, butyrate exhibited an effective prevention against SARS-CoV-2 by upregulating antiviral immune responses and promoting cell survival. IMPORTANCE Since SARS-CoV-2 has caused severe disease characterized by acute respiratory distress syndrome (ARDS) in humans, it is essential to develop therapeutics based on relieving such severe clinical symptoms. Current therapy strategies mainly focus on individuals who have COVID-19, however, there is still a strong need for prevention and treatment of SARS-CoV-2 infection. This study showed that butyrate, a bacterial metabolite, improved the response of SARS-CoV-2-infected hamsters by reducing immunopathology caused by impaired antiviral defenses and inhibiting excessive apoptosis through reduction in oxidative stress.