. 2022 Aug 31;13(19):2681–2691. doi: 10.1111/1759-7714.14626

TABLE 1.

Current data on microbiota and irAEs

Reference	Species	Disease	Intervention	irAE organ affected	Microbiota analysis method	Significant outcome	Potential mechanism
Chaput et al. ¹⁸	26 patients	Metastatic melanoma	Anti‐CTLA‐4	Colitis	16 s rRNA	Baseline phyla level: enriched Firmicutes in patients with colitis, high proportions of Bacteroidetes in patients without colitis 15 bacterial OTUs were detected as potential biomarkers of colitis onset. 5/6 OTUs (e.g., B. uniformis, B. vulgatus, Parabacteroides distasonis, Prevotella) from the Bacteroidetes phylum were associated with an absence of colitis. 8/9 OTUs (e.g., Faecalibacterium prausnitzii, Gemmiger formicilis, Roseburia inulinivorans, Fusicatenibacter saccharivorans, Blautia obeum, Clostridiales bacterium, butyrate‐producing bacteria from the Firmicutes phylum) were associated with colitis.	Low proportion of peripheral blood regulatory T cells (Tregs), α4⁺β7⁺ CD4⁺ T cells, and α4⁺β7⁺ CD8⁺ T cells in patients enriched with Faecalibacterium and other Firmicutes. Patients with irAE colitis tended to have significantly higher CD4⁺ T cells, IL‐6, IL‐8 and sCD25. Higher inducible T cell costimulator induction on CD4⁺ T cells and serum CD25 in patients who enriched with Faecalibacterium.
Chaput et al. ¹⁸	26 patients	Metastatic melanoma	Anti‐CTLA‐4	Colitis	16 s rRNA
Dubin et al. ²³	34 patients	Metastatic melanoma	Anti‐CTLA‐4	Colitis	16 s rRNA; shotgun sequencing	Patients with or without colitis shared many bacterial taxa belonging to the Firmicutes phylum. Patients without colitis harbored a greater proportion of the Bacteroidaceae family. Patients without colitis had a higher abundance of Bacteroidaceae, Rikenellaceae, and Barnesiellaceae from the Bacteroidetes phylum.	Genetic pathways involved in polyamine transport and B vitamin biosynthesis were associated with an increased risk of colitis.
Liu et al. ²⁴	26 patients	Advanced lung cancer	Anti‐PD‐1	Colitis	16 s rRNA	Species abundance and diversity tended to be lower in patients with diarrhea/colitis, but without a statistical difference. Firmicutes and Bacteroidetes phylum were the most abundant in patients with or without diarrhea/colitis, respectively. Probable risk factors for diarrhea/colitis: Bacteroides and Parabacteroides from the Bacteroidetes phylum, Phascolarcto bacterium from the Firmicutes phylum, and Veillonella from the Proteobacteria phylum.	NA
Chau et al. ²⁰	13 patients	Lung cancer	Anti‐PD‐1/PD‐L1	Rash/colitis/myositis/pneumonitis/thrombocytopenia	16 s rRNA	Enrichment of Bifidobacterium of Actinobacteria phylum and Desulfovibrio of Proteobacteria phylum were significantly associated with lower incidence and grade of irAEs.	NA
SaKai et al. ²⁵	18 patients	Lung/stomach/kidney/ovary cancer	ICIs	Colitis	16 s rRNA	Decreased abundance of Bacteroides species and enriched Enterobacteria in inflamed regions of irAE colitis.	Pathways associated with molecular transport systems, including fatty acids, were enriched in irAE colitis.
McCulloch et al. ²⁶	57 patients	Melanoma	Anti‐PD‐1	Pneumonitis/colitis/hepatitis/nephritis/arthritis/throid/adrenal/dermatologic/neurologic	16 s rRNA	Enriched for Lachnospiraceae spp. and Streptococcus spp.	NA

Abbreviations: CTLA‐4, cytotoxic T lymphocyte antigen‐4; ICIs, immune checkpoint inhibitors; irAEs, immune‐related adverse events; NA, not applicable; OTUs, operational taxonomic units; PD‐1, programmed cell death‐1; qPCR, quantitative polymerase chain reaction; TNBS, 2,4,6‐trinitrobenzene sulfonic acid.