# Interventions Targeting the Gut Microbiome to Improve Cancer Treatment Outcomes and Their Gastrointestinal Side Effects: A Systematic Review and Meta-analysis

## TL;DR

This study reviews how gut microbiome interventions can reduce gastrointestinal side effects in cancer treatment, but their impact on treatment outcomes remains unclear.

## Contribution

A systematic review and meta-analysis showing gut microbiome interventions reduce gastrointestinal adverse events in cancer therapy.

## Key findings

- Gut microbiome interventions reduced gastrointestinal adverse events with a relative risk of 0.59.
- No significant improvement in objective disease response rates was observed.
- High heterogeneity suggests variability in intervention effectiveness across studies.

## Abstract

Improvements in cancer treatment are essential to reduce premature mortality. Emerging evidence highlights the role of the gut microbiome (GM) in influencing treatment responses and modulating gastrointestinal adverse events (GIAEs). Because cancer therapy disrupts GM composition, restoring gut health may help mitigate side effects and support gut-associated immunity.

This study aimed to systematically evaluate and assess the effectiveness of GM interventions on the occurrence of GIAEs and clinical responses to cancer treatment.

Three databases (PubMed, Web of Science, and Cochrane Library) were systematically searched up to February 2025 for studies assessing GM interventions during cancer treatment. Risk of bias was evaluated using the Effective Public Healthcare Panacea Project Quality Assessment tool. Meta-analyses were conducted in Stata 18 using random-effects models to estimate the pooled relative risk of GM interventions on gut microbiome interventions, gastrointestinal adverse events (GIAEs) (primary outcome) and objective disease response rates (secondary outcome).

Fifty-six studies were included in the systematic review, and 40 were meta-analyzed (n = 37 for GIAE outcomes, n = 8 for treatment response). GM interventions reduced the overall risk of GIAEs [relative risk (RR)]: 0.59; 95% CI: 0.53, 0.65; I2: 76.8%; 95% prediction interval (PI): 0.32, 1.08], including diarrhea, constipation, nausea, and vomiting, but with considerable heterogeneity between studies. There was insufficient evidence to suggest improvements in objective disease response rates (RR: 1.06; 95% CI: 0.93, 1.20; I2: 0%; 95% PI: 0.93, 1.20).

GM interventions show promise in improving cancer care by reducing GIAEs, although evidence for direct effects on-treatment response remains limited. Standardizing intervention protocols and outcome reporting in future RCTs is essential to strengthen the evidence base and guide clinical recommendations.

This trial was registered at PROSPERO as CRD42023443332 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023443332).