Intest Res.  2021 Oct;19(4):360-364. 10.5217/ir.2020.00116.

Gut microbiome and checkpoint inhibitor colitis

• Sehgal K
• Khanna S

• KMID: 2521599
• DOI: http://doi.org/10.5217/ir.2020.00116

Abstract

Immune checkpoint inhibitor therapies such as ipilimumab, are increasingly being used as a treatment option for a variety of cancers, including metastatic melanoma and have demonstrated effectively a prolonged survival. These agents have an immunological mode of action that predisposes patients to a number of immune-related adverse events, colitis being one of the most commonly encountered complications. The pathogenesis for the development of colitis is unclear, and there is a growing consensus that the ecosystem of the gastrointestinal microbiota plays a significant role. Based on this suspected connection, studies are being carried out to explore the changes in the microbiota in patients on these medications who develop colitis. Conceivably, the modulation of the gut microbiota could offer a therapeutic benefit. Fecal microbiota transplantation is one therapeutic option that is currently being investigated, though there are still more data needed to evaluate its efficacy. In this review, we recapitulate the mechanisms of action of immune checkpoint inhibitors, their adverse events, with a focus on colitis and the role gut microbiota are suspected to play, and finally discuss the microbiota modulation therapies being investigated.

Keyword

Colitis; Neoplasms; Checkpoint inhibitor; Diarrhea; Biota

Figure

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  Fig. 1 Management algorithm for ICI-induced colitis. aGrade 1: increase of <4 stools/day from baseline and grade 2: increase of 4–6 stools/day from baseline; bGrade 3: increase of ≥7 stools/day; hospitalization indicated and grade 4: life threatening consequences; urgent intervention indicated; cHigh risk features: grade 1 or 2 diarrhea or grade 3 or 4 diarrhea with the following signs or symptoms: moderate to severe cramping, decreased performance status, fever, sepsis, neutropenia, frank bleeding or dehydration23; dIntravenous methyl-prednisone is first line therapy for severe diarrhea until stabilization (3 days to 2 weeks) followed by oral prednisone dose tapered over 6–8 weeks.3 ICI, immune checkpoint inhibitor; CBC, complete blood count; CMP, comprehensive metabolic panel; irAEs, immune-related adverse events; CT, computed tomography; CTCAE v5.0, Common Terminology Criteria for Adverse Events: version 5.0 for diarrhea and colitis22; GI, gastrointestinal; TNF, tumor necrosis factor.

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