晚期恶性肿瘤患者发生免疫相关不良事件时的肠道微生物组成。

Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.

机构信息

Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.

Eight-year Medical Doctor Program, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.

出版信息

Front Immunol. 2023 Feb 20;14:1109281. doi: 10.3389/fimmu.2023.1109281. eCollection 2023.

INTRODUCTION

The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.

METHODS

From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.

RESULTS

Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (=0.003). , , and were less abundant and more abundant in irAE patients, while and were less abundant and more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).

CONCLUSIONS

The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

简介

肠道微生物群与免疫相关不良事件（irAEs）的发生和严重程度有关，但它的作用及其与 irAEs 的因果关系尚未确定。

方法

2020 年 5 月至 2021 年 8 月，前瞻性收集了 37 例接受抗 PD-1 治疗的晚期胸部恶性肿瘤患者的 93 份粪便样本，以及 33 例发生不同 irAEs 的各种癌症患者的 61 份样本。进行 16S rDNA 扩增子测序。接受抗生素治疗的小鼠接受来自无结肠炎 irAE 患者和有结肠炎 irAE 患者粪便样本的粪便微生物群移植（FMT）。

结果

irAE 患者与无 irAE 患者（P=0.001）和无结肠炎型 irAE 患者与有结肠炎型 irAE 患者（=0.003）的微生物群组成存在显著差异。irAE 患者中，、、丰度较低，丰度较高，而结肠炎型 irAE 患者中、丰度较低，丰度较高。irAE 患者中主要的丁酸产生菌也比无 irAE 患者（P=0.007）和无结肠炎 vs. 结肠炎 irAE 患者（=0.018）少。irAE 预测模型在训练中的 AUC 为 86.4%，在测试中的 AUC 为 91.7%。在结肠炎 irAE-FMT（3/9）小鼠中，免疫相关结肠炎比非 irAE-FMT 小鼠（0/9）更常见。