Impact of TLR5 overexpression on gut microbiota and metabolites: Insights into Salmonella infection outcomes.

BACKGROUND

The gut microbiome and the host immune system work together to maintain intestinal health and protect against infections. Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and plays a crucial role in this network. However, the precise role of TLR5 in regulating gut microbiota and resistance to infection remains unclear. This study utilized a TLR5 intestine-specific overexpression mouse model to explore these interactions and their impact on Salmonella infection.

METHODS

TLR5 intestine-specific overexpression mice (TLR5+/+) and wild-type (WT) mice were infected with Salmonella to assess TLR5's protective role. Survival time, fecal Salmonella load, and intestinal tissue integrity were evaluated. Subsequently, 16S rRNA sequencing and LC-MS-based metabolomics were performed to analyze gut microbiota composition and fecal metabolites. Fecal microbiota transplantation (FMT) and metabolite transplantation experiments were conducted to evaluate the functional impact of microbiota and metabolites on resistance to infection.

RESULTS

TLR5 overexpression significantly improved survival time and reduced fecal Salmonella load, demonstrating its protective role against infection. 16S rRNA sequencing revealed enrichment of beneficial taxa, while metabolomic analysis identified altered metabolites in TLR5+/+ mice. Although fecal microbiota and metabolite transplantation did not fully replicate the protective effects, these experiments highlighted the important roles of microbiota and metabolites in infection outcomes, with limitations in transplantation likely affecting the results. These findings underscore the significance of microbiota and metabolites in TLR5-mediated gut immunity.

CONCLUSION

TLR5 overexpression significantly alters gut microbiota and metabolite profiles, contributing to improved infection outcomes. These findings highlight the critical roles of microbiota and metabolites in TLR5-mediated immunity and provide a foundation for exploring targeted strategies to enhance resistance against enteric pathogens.