Examining the Effect of Indole-3-Propionic Acid in Antiviral and Repair Function Across Human Epithelium

Abstract

Barrier tissues, such as the vaginal and intestinal mucosa, are in constant contact with the environment and thus must coordinate host defense and tissue repair to maintain homeostasis. Microbiota-derived metabolites have emerged as important regulators of these processes, yet their tissue-specific effects remain poorly defined. This study investigates the role of indole-3-propionic acid (IPA), a tryptophan-derived microbial metabolite, in modulating antiviral signaling and epithelial repair across distinct mucosal environments. Using primary human vaginal and small intestinal epithelial cell models, as well as an in vivo murine system, I examined how IPA influences antiviral defense and tissue repair dynamics. IPA consistently upregulated interferon-stimulated genes and increased interferon-β production, but the magnitude and timing of these responses differed by tissue. Vaginal epithelial cells exhibited rapid and high amplitude antiviral responses, while small intestinal epithelial cells showed moderate and sustained activation. IPA also enhanced wound repair in both tissues in a dose-dependent manner. Vaginal wounds closed rapidly and showed IPA-dependent acceleration starting at 6 hours. Intestinal wounds required longer to resolve, but IPA effects emerged as early as 3 hours. Transcriptional analyses revealed tissue-specific repair signatures, with IPA upregulating ITGA6 in vaginal cells and LGR5 in intestinal cells, suggesting distinct mechanisms of regeneration. Although the in vivo norovirus challenge yielded inconclusive results, therefore limiting assessment of IPA’s effects in physiological settings, the in vitro findings demonstrate that IPA acts as a multifunctional and context-dependent modulator of mucosal barrier function. This work highlights IPA as a promising candidate for future therapeutic strategies aimed at strengthening barrier integrity and mucosal immunity.