Gut microbiota and immunotherapy response: A round-up of the trials
The gut microbiome has emerged as an unlikely influencer of response to treatment with immune checkpoint inhibitors across various tumor types. Here we provide a brief summary of the key studies – all published in Science – that have investigated this association.
The two earlier studies in mice and the three recent ones involving patients all showed that the constitution of the gut microbiome is a crucial factor in determining the efficacy of immunotherapeutic agents, with specific bacterial species shown to have a role.
In addition, two of the three studies in humans found that the microbiota diversity was higher among patients who responded to immunotherapy than those who did not. Finally, all three studies showed that fecal transfer from responding and nonresponding patients to various mouse models of cancer mimicked the patient phenotype in the animals.
Read on for details of the main findings from these studies.
Key findings from the studies in patients
Bacterial species enriched in responders
Bacterial species enriched in nonresponders
Routy et al 
Advanced NSCLC or RCC
Firmicutes; Akkermansia muciniphila
Clostridiales order; Ruminococcaceae family; Faecalibacterium genus
Bacteroidales order, including Bacteroides thetaiotaomicron and Anaerotruncus colihominis; Escherichia coli
Matson et al 
Anti-PD-1 mainly, but anti-CTLA-4 in four patients
Enterococcus faecium; Collinsella aerofaciens; Bifidobacterium adolescentis; Klebsiella pneumoniae; Veillonella parvula; Parabacteroides merdae; Lactobacillus spp.; Bifidobacterium longum
Ruminococcus obeum, Roseburia intestinalis
Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; NSCLC, non-small-cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; RCC, renal cell carcinoma
Key findings from the studies in mouse models
Bacterial species associated with efficacy
Vétizou et al 
Sarcoma, melanoma, and colon cancer
Bacteroides spp., including Bacteroides fragilis and Bacteroides thetaiotaomicron; Burkholderia cepacia
Sivan et al 
Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; NSCLC, non-small-cell lung cancer; PD-L1, programmed cell death ligand 1; RCC, renal cell carcinoma
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- Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 2018; 359: 91–97.
- Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 2018; 359: 97–103.
- Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science 2018; 359: 104–108.
- Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015: 350, 1079–1084.
- Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 2015: 350, 1084–1089.