AUTHOR=Liu Xinyu , Tang Hao , Zhou Qingyang , Zeng Yanlin , Lu Bo , Chen Dan , Li Yue , Qian Jiaming , Chen Minjiang , Zhao Jing , Xu Yan , Wang Mengzhao , Tan Bei 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1109281

DOI=10.3389/fimmu.2023.1109281

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (<italic>P</italic>=0.003). <italic>Bifidobacterium</italic>, <italic>Faecalibacterium</italic>, and <italic>Agathobacter</italic> were less abundant and <italic>Erysipelatoclostridium</italic> more abundant in irAE patients, while <italic>Bacteroides</italic> and <italic>Bifidobacterium</italic> were less abundant and <italic>Enterococcus</italic> 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 (<italic>P</italic>=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).</p></sec><sec><title>Conclusions</title><p>The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.</p></sec>