Associations between baseline gut microbiota and GI immune-related adverse events, as well as antitumour response in human patients
| References | Patients | Methods | Bacteria associated with antitumour response | Bacteria associated with non-response | Bacteria associated with GI irAE | Metabolomics results |
| Chaput et al 84 | 26 MM patients treated with ipi | PCR 16S | Firmicutes Faecalibacterium prausnitzii L2-6, butyrate producing bacterium L2-21, Gemmiger formicilis ATCC 27749 | Bacteroidetes (mostly Bacteroides genus) | Colitis: Firmicutes No colitis: Bacteroidetes (mostly Bacteroides genus) | NA |
| Dubin et al 98 | 34 MM patients treated with ipi | PCR 16S | NA | NA | Colitis-free: Bacteroidetes | Spermidine/putrescine polyamine transport Biosynthesis of B1, B2 and B5 vitamins* |
| Frankel et al 99 | 39 MM patients treated with anti-PD-1 (n=14), ipi (n=1) or both (n=24) | Metagenomic shotgun sequencing | F. prausnitzii, Bacteroidesthetaiotaomicron, Holdemania filiformis in responders to ipi/nivo combination | NA | NA | ICI responders: fatty acid synthesis * Increased anacardic acid levels † Responders to ipi/nivo combination therapy: inositol phosphate metabolism* |
| Routy et al 100 | 249 patients with NSCLC, RCC or urothelial carcinoma treated with anti-PD-1 | Metagenomic shotgun sequencing | Firmicutes, Akkermansia, Alistipes, Decreased Bifidobacterium adolescentis Bifidobacterium longum Parabacteroides distasonis | NA | NA | NA |
| Gopalakrishnan et al 101 | 89 MM patients treated with anti-PD-1 | Metagenomic shotgun sequencing | Gut microbiota diversity Clostridiales Faecalibacterium genus | Bacteroidales B. thetaiotaomicron, Escherichia coli Anaerotruncus colihominis | NA | NA |
| Matson et al 102 | 42 MM patients treated with anti-PD-1 | PCR 16S, metagenomic shotgun sequencing qPCR | Enterococcus faecium, Collinsella aerofaciens, Bifidobacterium adolescentis, Klebsiella pneumoniae, Veillonella parvula, Parabacteroides merdae, Lactobacillus sp | Bifidobacterium longum, Ruminococcus obeum, Roseburia intestinalis | NA | NA |
*Conversion of shotgun sequencing reads of baseline gut microbiota into relative abundances metabolic modules.130 131
†Using ultrahigh performance liquid chromatography-tandem mass spectroscopy.
GI irAE, GI immune-related adverse effects; ICI, immune checkpoint inhibitor; ipi, ipilimumab; MM, melanoma; NSCLC, non-small-cell lung carcinoma; PD-1, programmed death-1; RCC, renal carcinoma; NA, not addressed; nivo, nivolumab.