Microbiota-derived short chain fatty acids: Their role and mechanisms in viral infections

Abstract

Microbiota-derived short-chain fatty acids (SCFAs) are crucial for protecting the intestinal barrier and regulating the immune response during infections. Recent studies show that viral infections alter the local microbiota and SCFA synthesis, and there is mounting evidence linking low SCFA levels in individuals with an increased risk of contracting viral infections. Based on the type of the virus, SCFAs may have either antiviral or pro-viral activity. Butyrate, for instance, prevents tissue injury caused by neutrophil infiltration into the airways, which occurs when mice are infected with influenza. Bone marrow-derived free fatty acid receptor 3 (FFAR3) is induced by butyrate and leads to the conversion of monocytes into alternatively activated macrophages (AAMs) instead of proinflammatory macrophages, which in turn reduces neutrophil recruitment in the lung. Treatment with SCFA butyrate increased CD8 + T cell responsiveness to the influenza virus by enhancing their metabolism and functional activity. In addition, SCFAs may control interferon (IFN) responses to viral diseases. Microbiota-derived acetate may inhibit respiratory syncytial virus (RSV) by boosting IFN-β in a G-protein-coupled receptor 43 (GPR43)-dependent way. Injection of SCFA-producing Lachnospiraceae or exogenous acetate into mice reduces RSV pulmonary viral load, prevents recruitment of inflammatory cells in the lung, and increases animal survival. It has been shown that butyrate and propionate both provide comparable safeguards. Increased NF-kappa B (NF-kB) p65 translocation into the nucleus in response to acetate administration provides scientific proof that NF-kB activation is implicated in the connection between GPR43 interaction and IFN-β production; however, this mechanism requires additional investigations. In this article, we will critically analyze the function of SCFAs during various viral infections, discussing and summarizing the many impacts and action mechanisms of SCFAs.