Inhibition of PD-1 Protects against TNBS-Induced Colitis via Alteration of Enteric Microbiota

Background and Aim. The enteric microbiota is able to cross-talk with factors involved in the blockade of programmed cell death protein 1 (PD-1) and also plays an important role in the predisposition and onset of inflammatory bowel disease (IBD). The current study used a mouse model of experimental colitis to determine the pathogenic connection between PD-1 inhibition, gut microbiota, and IBD. Methods. Colitis was induced in mice using 2,4,6-trinitrobenzene-sulfonic acid (TNBS), and mice were subsequently treated with either a PD-1 inhibitor or 5-amino-salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high-throughput 16S rRNA sequencing of fecal samples from the experimental mice. Results. TNBS caused mice to experience IBD-like symptoms, which were attenuated by the PD-1 inhibitor, as indicated by a decrease in DAI scores (p=0.0002). Furthermore, in this mouse model of IBD, PD-1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short-chain fatty acid- (SCFA-) producing bacteria of the Firmicutes (p<0.05) and Bacteroidetes (p<0.05) phyla but depopulated Proteobacteria (p<0.05). Conclusion. PD-1 inhibition can partly mitigate TNBS-induced colitis and restore the enteric microbiota by enriching the abundance of SCFA-producing bacteria.

Automated summary

In this study, the relationship between PD-1 inhibition, gut microbiota, and IBD was investigated using a mouse model of experimental colitis. The results demonstrated that PD-1 inhibition attenuated colitis symptoms, improved the diversity of the enteric microbiome, and enriched the abundance of SCFA-producing bacteria.