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


ABSTRACT:

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.

SUBMITTER: Xu HM 

PROVIDER: S-EPMC7810563 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Xu Hao-Ming HM   Zhou You-Lian YL   Xu Jing J   Li Ying-Fei YF   Zhao Chong C   Huang Hong-Li HL   Du Yan-Lei YL   He Jie J   Zhou Yong-Jian YJ   Nie Yu-Qiang YQ  

BioMed research international 20210107


<h4>Methods</h4>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.<h4>Results</h4>TNBS caused mice to experience IBD-like symptoms, whic  ...[more]

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