Targeting the Gut Microbiome to Mitigate Immunotherapy-Induced Colitis in Cancer

Amy E Chang; Jonathan L Golob; Thomas M Schmidt; Daniel C Peltier; Christopher D Lao; Muneesh Tewari

doi:10.1016/j.trecan.2021.02.005

Targeting the Gut Microbiome to Mitigate Immunotherapy-Induced Colitis in Cancer

Trends Cancer. 2021 Jul;7(7):583-593. doi: 10.1016/j.trecan.2021.02.005. Epub 2021 Mar 16.

Authors

Amy E Chang¹, Jonathan L Golob², Thomas M Schmidt³, Daniel C Peltier⁴, Christopher D Lao⁵, Muneesh Tewari⁶

Affiliations

¹ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
² Department of Internal Medicine, Division of Infectious Disease, University of Michigan, Ann Arbor, MI, USA.
³ Department of Internal Medicine, Division of Infectious Disease, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA; Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Pediatrics, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: clao@med.umich.edu.
⁶ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: mtewari@med.umich.edu.

PMID: 33741313
DOI: 10.1016/j.trecan.2021.02.005

Abstract

Immune checkpoint inhibitors (ICIs) have been a transformational advance in cancer therapy in the past decade. However, ICIs can produce immune-related adverse effects (irAEs), which can lead to both morbidity and premature termination of therapy. Recent studies suggest that the gut microbiota and its metabolites affect ICI efficacy and toxicity. Herein, we review such evidence in the context of ICI-induced colitis. In particular, the short-chain fatty acid butyrate, a microbial metabolite, has known protective effects on the intestine. We discuss how the use of dietary prebiotics, which can be metabolized by bacteria to produce butyrate, can be an intriguing new investigational approach to prevent ICI-associated colitis and lead to improved patient outcomes.

Keywords: butyrate; cancer; colitis; immunotherapy; microbiome; prebiotic; resistant starch; toxicity.

Publication types

Review

MeSH terms

Animals
Butyrates / metabolism
Colitis / chemically induced
Colitis / immunology
Colitis / microbiology
Colitis / prevention & control*
Disease Models, Animal
Gastrointestinal Microbiome / immunology*
Humans
Immune Checkpoint Inhibitors / adverse effects*
Mice
Neoplasms / drug therapy*
Neoplasms / immunology
Prebiotics / administration & dosage*

Substances

Butyrates
Immune Checkpoint Inhibitors
Prebiotics