Lactobacillus rhamnosus confers protection against enteropathogenic bacteria by enhancing mucosal immunity and epithelial barrier function

Lactobacillus rhamnosus (L. rhamnosus) has a long history of application in the food and beverage industry and is recognized as an important probiotic strain with immunomodulator activities against bacteria infection. However, the mechanisms by which L. rhamnosus protects against enteric bacterial infection are not fully understood. In this study, using the L. rhamnosus isolate CIQ249, we investigated the potential mechanisms through which L. rhamnosus, as a microecological agent, regulates intestinal homeostasis to antagonize enteropathogenic bacterial infection. We found that metabolites from CIQ249 significantly inhibited the growth of enteropathogenic bacteria. Treatment with CIQ249 effectively alleviated intestinal mucosal injury in mice infected with pathogenic bacteria by enhancing tight junction proteins (ZO-1 and Claudin-1)-regulated the integrity of intestinal epithelial tight junctions. Furthermore, oral administration of CIQ249 significantly promoted production of immune-related cytokines, enhanced differentiation of CXCR5+CD4+T lymphocytes, increased the proliferative capacity of B lymphocytes, and further drove their differentiation into IgA-secreting plasma cells. RNA-seq analysis revealed significant changes in the expression of the genes involved in anti-infection immunity. The CIQ249 also demonstrated strong intestinal colonization capacity and conferred multiple beneficial effects. In conclusion, the strain CIQ249 enhances both the physical and immune barriers of the intestine to resist bacterial infection. The CIQ249 is proposed as a promising candidate for the development of microecological agents.