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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review
Oliver Oey, Yu-Yang Liu, Angela Felicia Sunjaya, Daniel Martin Simadibrata, Muhammad Adnan Khattak, Elin Gray
Oliver Oey, Department of Medical Oncology, St John of God Midland Public and Private Hospital, Midland, Perth 6004, WA, Australia
Oliver Oey, School of Medicine, University of Western Australia, Perth 6009, WA, Australia
Yu-Yang Liu, School of Medicine, University of Queensland, Brisbane 4072, QLD, Australia
Angela Felicia Sunjaya, Faculty of Medicine, Tarumanagara University, Jakarta 11440, Indonesia
Daniel Martin Simadibrata, School of Medicine, University of Indonesia, Jakarta 10430, Indonesia
Muhammad Adnan Khattak, Department of Medical Oncology, Fiona Stanley Hospital, Perth 6150, WA, Australia
Muhammad Adnan Khattak, Elin Gray, School of Medical Sciences, Edith Cowan University, Perth 6027, WA, Australia
Muhammad Adnan Khattak, Elin Gray, Centre for Precision Health, Edith Cowan University, Perth 6027, WA, Australia
Author contributions: Oey O, Simadibrata DM, Gray E and Khattak MA contributed to the study conception and design; Oey O and Liu Y performed data extraction; Oey O and Simadibrata DM performed risk of bias assessment; Oey O, Liu Y, Sunjaya AF, Simadibrata DM, Khattak MA and Gray E performed data analysis; Oey O written the first draft of the manuscript; all authors commented on previous versions of the manuscript, read and approved the final manuscript.
Conflict-of-interest statement: Khattak MA reports receiving travel support from Merck Sharp and Dohme (MSD), Bristol-Myers Squibb and Merck Serono. Gray E reports receiving travel sponsorship from MSD. Oey O, Liu Y, Sunjaya AF, and Simadibrata DM report no competing interests.
PRISMA 2009 Checklist statement: All authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Oliver Oey, MD, Doctor, Researcher, Department of Internal Medicine, St John of God Midland Public and Private Hospital, Midland, No. 1 Clayton Street, Perth 6004, WA, Australia. oliver.oey@sjog.org.au
Received: October 19, 2022
Peer-review started: October 19, 2022
First decision: October 28, 2022
Revised: October 30, 2022
Accepted: November 6, 2022
Article in press: November 6, 2022
Published online: November 24, 2022
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.
Core Tip: Since the introduction of immune checkpoint inhibitors as part of standard of care for melanoma patients, there has been a growing interest in identifying biomarkers of response and immune related adverse events. Amongst these biomarkers, the composition of the gut microbiome has been one of the most intriguing discoveries. Our aim was to ascertain the current published evidence on the gut microbiome diversity and composition as a biomarker of response to immunotherapy. We demonstrated high variability in the results and limited concordance on the organisms identified. We highlight the conflicting aspects of these reports as well as their few commonalities.
