# Immune-Mediated Colitis Induced by Immune Checkpoint Inhibitors: Pathophysiology, Clinical Management, and the Emerging Role of Fecal Microbiota Transplantation

## TL;DR

This review discusses immune-mediated colitis caused by cancer treatments and explores new strategies like fecal microbiota transplantation for managing it.

## Contribution

The paper highlights the emerging role of fecal microbiota transplantation in treating immune-mediated colitis.

## Key findings

- IMC is driven by immune activation, cytokine release, and gut microbiota changes.
- Corticosteroids are first-line therapy, while infliximab and vedolizumab help in steroid-resistant cases.
- Fecal microbiota transplantation shows promise for refractory immune-mediated colitis.

## Abstract

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT). Methods: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach. Results: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease. Conclusions: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice.