Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review

BACKGROUND: Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis. AIM: To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB. METHODS: The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). RESULTS: Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, P < 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis (P < 0.01) whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis (P < 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results. CONCLUSION: This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.