Efficacy and safety of fecal microbiota transplantation for chronic constipation: a systematic review and meta-analysis integrating pre-post and single-arm evidence.

BACKGROUND: Chronic constipation is a common functional gastrointestinal disorder with a global prevalence of 12%-17%. Conventional treatments have limited efficacy for refractory cases, with high recurrence and side effects. Fecal microbiota transplantation (FMT) offers a novel strategy by restoring gut microecological balance, yet its efficacy requires systematic evaluation. This meta-analysis evaluated FMT efficacy and safety through an innovative "three-in-one" framework. METHODS: We systematically searched CENTRAL, PubMed, Embase, and CNKI for RCTs, single-arm studies, and cohort studies. The framework comprised: (1) RCT random-effects meta-analysis; (2) single-arm proportional meta-analysis with Freeman-Tukey transformation; (3) pre-post paired sensitivity analysis (r = 0.5, with sensitivity tests at r = 0.3, 0.7, 0.9). Publication bias was assessed via Egger, Harbord, trim-and-fill, and fail-safe N tests. RESULTS: 12 RCTs (n = 1040), 16 single-arm studies (n = 403), and 4 cohort studies (n = 422) were included. After trim-and-fill adjustment for publication bias, FMT was associated with a clinical total response rate of RR = 1.21 (95% CI: 1.10-1.33). The unadjusted pooled estimate was RR = 1.36 (95% CI: 1.21-1.52, P < 0.001); however, the Harbord test indicated potential publication bias (P = 0.003), necessitating this correction. Wexner score improved (MD = -2.08, 95% CI: -3.35 to -0.81, P = 0.003). Among the 16 single-arm studies, 8 (n = 249) reported remission/improvement rates, showing a remission rate of 51.7% (95% CI: 40.3%-62.9%) and paired pre-post improvements in BSFS, Wexner, and PAC-QOL; these within-group changes cannot establish causal efficacy. During follow-up periods of up to 24 weeks, no serious adverse events were reported; long-term safety data are lacking. CONCLUSION: Current evidence suggests FMT is a promising therapeutic option for chronic constipation, with an adjusted clinical total response rate of RR = 1.21 (95% CI: 1.10-1.33) after correction for publication bias. While FMT was associated with improvements in symptom scores, quality of life, and intestinal function, the evidence quality is limited by publication bias, high heterogeneity, and high risk of bias in all included RCTs. More high-quality, sham-controlled RCTs are needed to validate these findings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261394673, identifier: CRD420261394673.