PMID- 33816289 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210406 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review. PG - 642110 LID - 10.3389/fonc.2021.642110 [doi] LID - 642110 AB - Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet. Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included. Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of "ICI-favoring" gut microbiome (P = 0.0476). Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome. CI - Copyright (c) 2021 Huang, Li, Liu, Zhu, Dai, Fan, Mehta, Huang, Neupane, Wang, Sun, Umar, Zhong and Zhang. FAU - Huang, Chengliang AU - Huang C AD - Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Li, Meizhang AU - Li M AD - Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States. FAU - Liu, Ben AU - Liu B AD - Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS, United States. FAU - Zhu, Huanbo AU - Zhu H AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. AD - Department of Gastrointestinal Surgery, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Dai, Qun AU - Dai Q AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Fan, Xianming AU - Fan X AD - Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China. FAU - Mehta, Kathan AU - Mehta K AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Huang, Chao AU - Huang C AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Neupane, Prakash AU - Neupane P AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Wang, Fen AU - Wang F AD - Department of Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States. FAU - Sun, Weijing AU - Sun W AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. FAU - Umar, Shahid AU - Umar S AD - Department of Surgery, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States. AD - Department of Cancer Biology, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States. FAU - Zhong, Cuncong AU - Zhong C AD - Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS, United States. FAU - Zhang, Jun AU - Zhang J AD - Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States. AD - Department of Cancer Biology, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States. LA - eng PT - Systematic Review DEP - 20210318 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8012896 OTO - NOTNLM OT - antibiotics OT - cancer immunotherapy OT - diet OT - gut microbiome OT - immunotherapy OT - microbiota OT - modulating factors OT - solid tumors COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors JZ. EDAT- 2021/04/06 06:00 MHDA- 2021/04/06 06:01 PMCR- 2021/01/01 CRDT- 2021/04/05 06:08 PHST- 2020/12/15 00:00 [received] PHST- 2021/02/24 00:00 [accepted] PHST- 2021/04/05 06:08 [entrez] PHST- 2021/04/06 06:00 [pubmed] PHST- 2021/04/06 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.642110 [doi] PST - epublish SO - Front Oncol. 2021 Mar 18;11:642110. doi: 10.3389/fonc.2021.642110. eCollection 2021.