There is growing recognition that the gut microbiota plays a role in modulating cancer therapy outcomes. A recent systematic review synthesized findings from 22 observational studies evaluating relationships between fecal microbiota profiles and chemotherapy response, efficacy, and toxicity in cancer patients.
Across tumor types, distinctive bacterial taxa were associated with favorable or unfavorable outcomes. In lung cancer, higher abundances of Streptococcus mutans, Enterococcus casseliflavus, and Bacteroides correlated with improved response, while in gastrointestinal malignancies, Lactobacillaceae, Bacteroides fragilis, and Roseburia faecis were positively associated. Short-chain fatty acid producing genera such as Dorea and Roseburia emerged repeatedly as health-associated, potentially contributing to anti-inflammatory effects, intestinal homeostasis, and modulation of chemotherapy-related mucositis. Conversely, taxa such as Prevotella, Klebsiella pneumoniae, and Erysipelotrichaceae were linked to increased treatment toxicity.
Mechanistic evidence, largely from preclinical models, implicates microbial metabolites and pathways in modulating drug efficacy and tolerance. For instance, Fusobacterium nucleatum has been shown to promote chemoresistance in colorectal cancer via TLR4-mediated autophagy activation, while β-glucuronidase–producing bacteria can reactivate irinotecan’s toxic metabolite SN-38 in the gut. Other bacteria may inactivate or degrade chemotherapeutic agents such as doxorubicin and 5-FU.
Despite compelling associations, the authors emphasize that causality remains unproven. Limitations include small sample sizes, heterogeneous study designs, variable sequencing methodologies, and inadequate control for confounders such as diet, antibiotic use, and baseline comorbidities. Longitudinal sampling, standardized analytical methods, and stratification by relevant host and environmental factors are needed to move the field toward actionable clinical insights.