The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, the inventors used high-resolution shotgun metagenomics and targeted metabolomics analyses to characterize influenza-associated changes in the mouse gut microbiota’s composition and metabolism. Quantitative targeted metabolomics analysis of serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, indole-containing tryptophan metabolites, trimethylamine, and polyamines. The changes in microbiota-associated metabolites were correlated with changes in taxon abundances and levels of disease markers. For instance, the tryptophan metabolite indole-3-propionic acid (IPA) was correlated positively with some Bacillota species but negatively with Bacteroidales bacteria M7, the viral load, and inflammation markers. Given its marked fall during infection, the inventors tested the effects of IPA supplementation in diseased animals. This supplementation was associated with a lower viral load and lower levels of local (lung) and systemic inflammation during influenza. Taken as a whole, the results highlighted IPA as both an important metabolic modulator to disease severity and a potential biomarker of influenza outcomes.