Open Access

REVIEW

The Role of the Gut Microbiome in Clinical Outcomes of Colorectal Cancer: A Systematic Review (2020–2025)

Iara Santos¹, Joana Liberal^1,2, Paulo Teixeira^1,3,4, Diana Martins^1,2,5,6, Fernando Mendes^1,2,5,6,7,*

1 Coimbra Health School (ESTeSC), Polytechnic University of Coimbra, Coimbra, 3046-854, Portugal
2 H&TRC—Health & Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, 3045-043, Portugal
3 Pathology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3000-075, Portugal
4 Faculty of Medicine, University of Coimbra, Coimbra, 3004-535, Portugal
5 Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Biophysics Institute of Faculty of Medicine, University of Coimbra, Coimbra, 3045-043, Portugal
6 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, 3000-548, Portugal
7 European Association for Professions in Biomedical Sciences, Brussels, 1000, Belgium

* Corresponding Author: Fernando Mendes. Email:

(This article belongs to the Special Issue: Advances and Innovations in Colorectal Cancer Research and Treatment)

Oncology Research 2026, 34(3), 3 https://doi.org/10.32604/or.2025.070281

Received 12 July 2025; Accepted 16 December 2025; Issue published 24 February 2026

Abstract

Background: The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes. Methods: Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed. Results: Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor’s nature, and individual characteristics play critical roles in microbiome modulation. Conclusion: The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor’s nature, and individual characteristics as modulators, in order to optimize clinical outcomes.

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Supplementary Material

Supplementary Material File

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