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Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis

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Abstract

The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.

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References

  1. Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16:563–580.

    Article  CAS  Google Scholar 

  2. Abu-Sbeih H, Ali FS, Wang Y. Immune-checkpoint inhibitors induced diarrhea and colitis: a review of incidence, pathogenesis and management. Curr Opin Gastroenterol. 2020;36:25–32.

    Article  CAS  Google Scholar 

  3. Pezo RC, Wong M, Martin A. Impact of the gut microbiota on immune checkpoint inhibitor-associated toxicities. Ther Adv Gastroenterol. 2019;12:1756284819870911.

    Article  CAS  Google Scholar 

  4. Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of Immune checkpoint inhibitor-related adverse events: roles of the intestinal microbiome and Th17 cells. Front Immunol. 2019;10:2254.

    Article  Google Scholar 

  5. Carvalho FA, Koren O, Goodrich JK, et al. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe. 2012;12:139–152.

    Article  CAS  Google Scholar 

  6. Abu-Sbeih H, Ali FS, Luo W, Qiao W, Raju GS, Wang Y. Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. J Immunother Cancer. 2018;6:95.

    Article  Google Scholar 

  7. Abu-Sbeih H, Faleck DM, Ricciuti B, et al. Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease. J Clin Oncol. 2019. https://doi.org/10.1200/JCO.19.01674.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Morgan XC, Tickle TL, Sokol H, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13:R79.

    Article  CAS  Google Scholar 

  9. Frank DN, Robertson CE, Hamm CM, et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17:179–184.

    Article  Google Scholar 

  10. Anderson R, Rapoport BL. Immune dysregulation in cancer patients undergoing immune checkpoint inhibitor treatment and potential predictive strategies for future clinical practice. Front Oncol. 2018;8:80.

    Article  Google Scholar 

  11. Dubin K, Callahan MK, Ren B, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7:10391.

    Article  CAS  Google Scholar 

  12. Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28:1368–1379.

    Article  CAS  Google Scholar 

  13. Wang Y, Wiesnoski DH, Helmink BA, et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med. 2018;24:1804–1808.

    Article  CAS  Google Scholar 

  14. Png CW, Linden SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–2428.

    Article  CAS  Google Scholar 

  15. Wang F, Yin Q, Chen L, Davis MM. Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade. Proc Natl Acad Sci U S A. 2018;115:157–161.

    Article  CAS  Google Scholar 

  16. Jenq RR, Taur Y, Devlin SM, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:1373–1383.

    Article  Google Scholar 

  17. Vetizou M, Pitt JM, Daillere R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–1084.

    Article  CAS  Google Scholar 

  18. Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–1089.

    Article  CAS  Google Scholar 

  19. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105:16731–16736.

    Article  CAS  Google Scholar 

  20. Kang S, Denman SE, Morrison M, et al. Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis. 2010;16:2034–2042.

    Article  Google Scholar 

  21. Routy B, Gopalakrishnan V, Daillere R, Zitvogel L, Wargo JA, Kroemer G. The gut microbiota influences anticancer immunosurveillance and general health. Nat Rev Clin Oncol. 2018;15:382–396.

    Article  CAS  Google Scholar 

  22. Abu-Sbeih H, Herrera LN, Tang T, et al. Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis. J Immunother Cancer. 2019;7:242.

    Article  Google Scholar 

  23. Abu-Sbeih H, Ali FS, Naqash AR, et al. Resumption of immune checkpoint inhibitor therapy after immune-mediated colitis. J Clin Oncol. 2019;37:2738–2745. https://doi.org/10.1200/JCO.19.00320.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Yinghong Wang.

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YW is a consultant for Tillotts Pharma. HA-S declares no conflict of interest.

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Abu-Sbeih, H., Wang, Y. Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis. Dig Dis Sci 65, 797–799 (2020). https://doi.org/10.1007/s10620-020-06103-x

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