Effect of probiotic, prebiotic, and synbiotic supplementation on anemia in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

Anemia is common in hemodialysis patients and reduces quality of life. Gut dysbiosis may contribute. Biotic supplements (probiotics, prebiotics, synbiotics) could help, but evidence is uncertain. This review evaluated their effects on hemoglobin, hematocrit, ferritin, and TIBC. We searched PubMed, Scopus, Cochrane Central, and Google Scholar up to May 2026 (PRISMA 2020). We included randomized controlled trials that compared probiotics, prebiotics, or synbiotics with a placebo in hemodialysis patients. Primary outcome: hemoglobin. Secondary: hematocrit, ferritin, TIBC. Two reviewers screened studies, extracted data, and assessed bias risk independently using the Cochrane RoB 2 tool. We performed meta-analyses with a random-effects model. We evaluated the certainty of evidence using the GRADE framework. PROSPERO: CRD420261404639. Nine randomized controlled trials with 878 patients were included. Biotic supplementation did not significantly improve hemoglobin (MD = 0.56 g/dL, 95% CI = -0.21 to 1.32, P = 0.15; I² = 89%). It also did not significantly affect hematocrit (MD = -0.09%, 95% CI = -2.43 to 2.26, P = 0.94; I² = 51%), ferritin (MD = 11.65 ng/mL, 95% CI = -12.70 to 35.99, P = 0.35; I² = 26%), or TIBC (MD = -68.35 mg/dL, 95% CI = -139.18 to 2.48, P = 0.06; I² = 56%). Subgroup analysis showed that probiotic supplementation (3 studies, 148 patients) significantly increased hemoglobin (MD = 0.51 g/dL, 95% CI = 0.01 to 1.01, P = 0.04; I² = 0%). In contrast, synbiotic supplementation (4 studies, 168 patients) did not have a significant effect (MD = 0.14 g/dL, 95% CI = -0.46 to 0.74, P = 0.65; I² = 62%). Prebiotic supplementation (1 study, 162 patients) showed a significant increase, but this finding should be interpreted with caution. Sensitivity analysis that excluded the prebiotic study led to an overall null effect with lower variability (I² = 32%). The certainty of evidence was low for hemoglobin, hematocrit, and TIBC, and moderate for ferritin. Low-certainty evidence suggests probiotics may slightly improve hemoglobin in hemodialysis patients. Synbiotics do not appear effective. Prebiotics require further study. Larger, well-designed trials are needed to confirm these findings. Not applicable.