The indole-3-propionic acid-producing bacteria Clostridium sporogenes protects against influenza

Abstract Gut microbiota, especially bacterial metabolites, play a key role in protecting the lungs against respiratory infections such as influenza A virus (IAV). However, IAV infection can disrupt the gut microbiota, potentially increasing disease severity. Notably, reduced levels of the microbial tryptophan metabolite indole-3-propionic acid (IPA) impair viral control and promote pulmonary inflammation, thereby exacerbating IAV infection. In the current study, we investigated the potential protective effects of Clostridium sporogenes , a human anaerobic commensal and IPA producer previously shown to mitigate metabolic, inflammatory, and neurological disorders, but whose effects during respiratory infection remain unexplored. Relative to untreated mice, C. sporogenes supplementation was associated with less severe disease, lower pulmonary viral loads, and reduced lung inflammation. C. sporogenes administration modulated infection-induced gut dysbiosis and restored systemic IPA levels, which were positively correlated with reduced clinical scores and pulmonary viral loads. IPA and its analogues failed to exert direct antiviral effects in cell-based assays, suggesting indirect effects on immunity or other host-pathogen interactions. The pregnane X receptor, a xenosensor known to be activated by IPA, was not involved in the protection mediated by C. sporogenes . Lastly, administration of pasteurized C. sporogenes improved influenza outcomes, an effect that also correlated with IPA levels. Collectively, these findings suggest that C. sporogenes may represent a promising next-generation probiotic candidate for the prevention or mitigation of acute viral respiratory infections.