Short-chain fatty acids in viral infection: the underlying mechanisms, opportunities, and challenges

Viral infections can cause cellular pathway derangements, cell death, and immunopathological responses, leading to host inflammation. Short-chain fatty acids (SCFAs), produced by the microbiota, have emerged as a potential therapeutic for viral infections due to their ability to modulate these processes. However, SCFAs have been reported to have both beneficial and detrimental effects, necessitating a comprehensive understanding of the underlying mechanisms. This review highlights the complex mechanisms underlying SCFAs' effects on viral infection outcomes. We also emphasize the importance of considering how SCFAs' activities may differ under diverse contexts, including but not limited to target cells with different metabolic wiring, different viral causes of infection, the target organism/cell's nutrient availability and/or energy balance, and hosts with varying microbiome compositions.