Lactobacillus johnsonii Alleviates Immune Checkpoint Inhibitor-Associated Colitis by Modulating Macrophage Polarization, Th1/Treg Cell Balance, and Intestinal Barrier Function via the Tryptophan Metabolism-AhR Pathway

High Resolution Image Download MS PowerPoint Slide This study aimed to clarify the effect of Lactobacillus johnsonii ( L. johnsonii ) on immune checkpoint inhibitors (ICIs)-associated colitis and the efficacy of ICIs. Administration of L. johnsonii mitigated the severity of colitis in the experimental ICI-associated colitis model, along with a decrease in the proportions of M1 macrophages and Th1 cells and an increase in those of M2 macrophages and Tregs in the colon. L. johnsonii intervention upregulated the expression of tight junction proteins. L. johnsonii promoted tryptophan metabolism and the production of anti-inflammatory metabolites. Correlation analysis identified indole-3-acetic acid (IAA) as a significant anti-inflammatory tryptophan metabolite, and gavage of IAA alleviated ICI-associated colitis. After blocking the AhR pathway, the protective effect of L. johnsonii against ICI-associated colitis was abrogated. Notably, in the tumor-bearing ICI-associated colitis model, L. johnsonii potentiated the therapeutic efficacy of ICIs. These findings support the potential clinical applications of L. johnsonii for ICI-associated colitis.