PD-1 抑制通过改变肠微生物群预防 TNBS 诱导的结肠炎。

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

机构信息

Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

出版信息

Biomed Res Int. 2021 Jan 7;2021:4192451. doi: 10.1155/2021/4192451. eCollection 2021.

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 ( = 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 ( < 0.05) and ( < 0.05) phyla but depopulated ( < 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.

方法

采用 2,4,6-三硝基苯磺酸（TNBS）诱导小鼠结肠炎，随后用 PD-1 抑制剂或 5-氨基水杨酸（ASA）作为阳性对照进行治疗。评估体重、疾病活动指数（DAI）、结肠长度和组织损伤，并通过对实验小鼠粪便样本进行高通量 16S rRNA 测序来分析肠内微生物群。

结果

TNBS 导致小鼠出现类似 IBD 的症状，PD-1 抑制剂可减轻这些症状，DAI 评分降低（=0.0002）。此外，在这种 IBD 小鼠模型中，PD-1 抑制可提高α多样性并恢复肠内微生物组的β多样性。它还显著富集了短链脂肪酸（SCFA）产生菌的丰度，属于（<0.05）和（<0.05）门，但减少了（<0.05）门的丰度。