Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2

OBJECTIVES: CD4(+) T cells are the key to many immune–inflammatory diseases mediated by microbial disorders, especially inflammatory bowel disease (IBD). The purpose of this study was to explore how pathogenic and probiotic bacteria directly affect the T helper (Th)17 and T regulatory (Treg) cell balance among CD4(+) T cells to regulate inflammation. METHODS: Porphyromonas gingivalis (Pg; ATCC 33277) and Lactobacillus rhamnosus GG (LGG; CICC 6141) were selected as representative pathogenic and probiotic bacteria, respectively. Bacterial extracts were obtained via ultrasonication and ultracentrifugation. Flow cytometry, RT‐qPCR, ELISAs, immunofluorescence and a Quantibody cytokine array were used. The dextran sodium sulphate (DSS)‐induced colitis model was selected for verification. RESULTS: The Pg ultrasonicate induced the apoptosis of CD4(+) T cells and upregulated the expression of the Th17‐associated transcription factor RoRγt and the production of the proinflammatory cytokines IL‐17 and IL‐6, but downregulated the expression of the essential Treg transcription factor Foxp3 and the production of the anti‐inflammatory factors TGF‐β and IL‐10 via the TLR4 pathway. However, LGG extract maintained Th17/Treg homeostasis by decreasing the IL‐17(+) Th17 proportion and increasing the CD25(+) Foxp3(+) Treg proportion via the TLR2 pathway. In vivo, Pg‐stimulated CD4(+) T cells aggravated DSS‐induced colitis by increasing the Th17/Treg ratio in the colon and lamina propria lymphocytes (LPLs), and Pg + LGG‐stimulated CD4(+) T cells relieved colitis by decreasing the Th17/Treg ratio via the JAK‐STAT signalling pathway. CONCLUSIONS: Our findings suggest that pathogenic Pg and probiotic LGG can directly regulate the Th17/Treg balance via different TLRs.