Fecal Short-Chain Fatty Acids in Colorectal Cancer Patients Versus Healthy Controls: A Systematic Review and Meta-Analysis

<b>Background</b>: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. <b>Methods</b>: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). <b>Results</b>: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD -0.37; 95% CI -0.63 to -0.10; <i>p</i> = 0.006; I² = 0%) and butyrate (pooled SMD -0.59; 95% CI -1.10 to -0.07; <i>p</i> = 0.026; I² = 64.4%), whereas propionate did not differ significantly (pooled SMD -0.02; 95% CI -0.85 to 0.82; <i>p</i> = 0.971; I² = 89%). <b>Conclusions</b>: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC.