Functional impact of dietary chitin upon Listeria monocytogenes pathogenesis

Chitin, the second most abundant polymer in nature, is recognized for biocompatibility and diverse effects on microbes and the host. However, the role of dietary chitin against foodborne pathogens such as Listeria monocytogenes remains underexplored. Here, we show that chitin functions as an environmental signal that attenuates L. monocytogenes virulence and mitigates infection outcomes. Consistent with previous studies, exposure of L. monocytogenes to chitin resulted in downregulation of key virulence genes and we demonstrate that this is accompanied by reduced pathogenesis in intestinal epithelial cells. While chitin can act as a pathogen-associated molecular pattern, stimulation of murine macrophages revealed no excessive induction of IL-6 or TNF-α after 24 h, indicating that it does not provoke detrimental inflammatory responses. In vivo, dietary supplementation with chitin significantly reduced bacterial burden in faeces and secondary organs within 24 h post-infection. These protective effects were further enhanced when mice were challenged with chitin-pretreated bacteria, highlighting the combined importance of host nutritional context and pathogen pre-exposure. Chitin also modulated host responses, promoting early IL-6 production and selectively shaping gut microbiota, with enrichment of potentially beneficial genera such as Alistipes, Eubacterium, and Duncaniella and suppression of pro-inflammatory Prevotella. Transcriptomic analyses revealed that L. monocytogenes responds to chitin by upregulating virR and dltD, indicative of an envelope stress response, though no direct link between VirR and virulence gene downregulation was observed. These findings establish chitin as a dietary molecule that simultaneously modulates pathogen virulence, host immunity, and microbial ecology, representing a potential strategy to mitigate gastrointestinal infection.