Overexpression of tlr5 adrffects gut microbiota resistance to Salmonella infection
The gut microbiome and the host immune system interact synergistically to maintain intestinal health and defend against infections. Toll-like receptor 5 (TLR5), known for recognizing bacterial flagellin, plays a pivotal role in this regulatory network. Despite significant advances in understanding the gut microbiome and TLR5, the precise role of TLR5 in gut health and infection resistance remains unclear. This study aimed to elucidate the role of TLR5 in regulating gut microbiota and metabolites and their impact on resistance to Salmonella infection using a TLR5 intestinal-specific overexpression mouse model.Methods: Fecal microbiota and metabolite transplantation experiments were conducted using feces from TLR5-overexpressing mice (TLR5+/+ group) and wild-type mice (WT group) into C57 mice, creating four experimental groups: Flora-TLR5-C57, Metabolite-TLR5-C57, Flora-WT-C57, and Metabolite-WT-C57. Mice were infected with Salmonella, and various parameters including survival time, fecal Salmonella load, and alterations in gut microbiota and metabolites were assessed.Results: Despite notable shifts in gut microbiota composition and metabolite profiles induced by TLR5 overexpression, no significant differences in fecal Salmonella load or survival time were observed across the experimental groups. TLR5-overexpressing mice exhibited an enrichment of beneficial bacterial taxa and significant changes in metabolites; however, these alterations did not correlate with enhanced resistance to Salmonella infection.Conclusion: Our findings suggest that while TLR5 overexpression significantly modifies gut microbiota and metabolite profiles, these changes do not directly enhance resistance to Salmonella infection. The immune response to Salmonella is multifaceted and involves various components beyond the gut microbiota and metabolites. Further research is required to elucidate the detailed molecular pathways through which TLR5 influences infection outcomes and to explore potential combined therapeutic strategies for enhancing host defenses against enteric pathogens.