Microbiota modulation in colorectal cancer: A scoping review of its potential role in toxicity mitigation and treatment response.

INTRODUCTION

Colorectal cancer (CRC) treatment remains limited by gastrointestinal toxicity, heterogeneous therapeutic responses, and treatment resistance. The gut microbiota has emerged as a modifiable factor implicated in these outcomes, particularly chemotherapy-induced toxicity. Probiotics, prebiotics, and synbiotics have been investigated as adjunctive strategies to mitigate chemotherapy-related harm. However, whether the field is ready to extend its focus toward oncologic endpoints, including treatment response, recurrence, and survival, remains unclear.

METHODS

We conducted a scoping review following the Arksey and O'Malley framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidance. PubMed, EBSCOhost, Scopus, and CENTRAL were searched through 18 February 2026 for studies evaluating probiotic, prebiotic, or synbiotic interventions in adults with CRC receiving systemic therapy. Primary clinical studies and systematic reviews were eligible. Outcomes included treatment-related toxicity, microbial composition, inflammatory and immune markers, and oncologic endpoints.

RESULTS

Of 114 records screened, 16 studies were included, comprising 9 primary studies and 7 systematic reviews. Most studies evaluated probiotic-only regimens in patients receiving fluoropyrimidine- or oxaliplatin-based chemotherapy. The most consistent benefit was a reduction in chemotherapy-induced gastrointestinal toxicity, particularly diarrhea, mucositis, and nausea, along with improved treatment tolerance. Effects on microbial diversity, systemic inflammation, and immune parameters were inconsistent. Only 2 trials directly addressed oncologic outcomes: one reported significantly higher 6-, 12-, and 24-month survival in the probiotic arm, whereas another identified a microbiota-based classifier that predicted treatment response, with an area under the curve (AUC) of 0.95. However, neither trial comprehensively reported conventional oncologic endpoints such as objective response rate or progression-free survival. In addition, strain, dose, and timing varied widely across studies.

DISCUSSION: Microbiota modulation is a plausible and well-tolerated adjunctive strategy in CRC. However, current evidence remains largely anchored to toxicity mitigation, while oncologic endpoints remain underexamined. The field appears ready to move beyond a supportive-care framework and prospectively test whether microbiota-targeted adjuncts influence treatment response, recurrence, and survival. Probiotics, prebiotics, and synbiotics should not be treated as interchangeable interventions. Advancing this research agenda will require adequately powered, strain-specific trials with prespecified oncologic endpoints, embedded microbiome and biomarker readouts, and harmonized reporting.