Gang Hu, Yunfeng Yu, Xinyu Yang, Di Zhang, Mengqing Wang, Fan Li
Probiotics may improve anemia-related parameters and iron metabolism in Chinese children with IDA. However, the pooled increase in Hb remains below the minimal clinically important difference, and evidence on total adverse events remains inconclusive. Therefore, probiotics should be considered as an adjunct to oral iron supplementation rather than a standalone intervention. These findings should be interpreted with caution due to potential biases and the inclusion of only Chinese children.
OBJECTIVE: This meta-analysis, combined with trial sequential analysis (TSA), aimed to evaluate the effects of probiotics on hematologic parameters and iron-regulation biomarkers in Chinese children with iron deficiency anemia (IDA).
METHODS: Ten electronic databases were systematically searched for eligible studies published up to April 30, 2026. Meta-analyses were conducted using RevMan (version 5.3), and TSA was performed with TSA software (version 0.9.5.10 beta). Dichotomous and continuous outcomes were pooled as risk ratios (RRs) and mean differences (MDs), respectively. Publication bias was assessed using Egger's and Harbord's tests.
RESULTS: Twelve randomized controlled trials involving 1,342 children with IDA were included. In terms of efficacy, probiotics significantly increased hemoglobin (Hb) (MD 8.64 g/L, 95% CI 6.77-10.52), red blood cell (MD 0.47 × 1012/L, 95% CI 0.19-0.76), mean corpuscular hemoglobin concentration (MD 15.66 g/L, 95% CI 12.55-18.77), mean corpuscular volume (MCV) (MD 6.68 fL, 95% CI 4.69-8.67), mean corpuscular hemoglobin (MD 2.40 pg, 95% CI 1.57-3.22), and hematocrit (MD 3.36%, 95% CI 2.31-4.41), serum iron (MD 1.70 μmol/L, 95% CI 0.89-2.51), and serum ferritin (MD 5.62 μg/L, 95% CI 4.24-7.00), while significantly reducing transferrin levels (MD - 0.24 g/L, 95% CI -0.34 to -0.15). Regarding safety, probiotics significantly reduced the incidence of total adverse events (RR 0.52, 95% CI 0.28-0.97), with no significant effects observed on anorexia, nausea and vomiting, metallic taste, abdominal pain, diarrhea, or constipation. TSA demonstrated that all positive outcomes, except total adverse events, reached the required information size and were conclusive. No significant publication bias was detected for most outcomes. Although publication bias was observed for MCV, trim-and-fill analysis confirmed the robustness of the pooled effect estimate. The evidence certainty of all outcomes was low or very low.
CONCLUSION: Probiotics may improve anemia-related parameters and iron metabolism in Chinese children with IDA. However, the pooled increase in Hb remains below the minimal clinically important difference, and evidence on total adverse events remains inconclusive. Therefore, probiotics should be considered as an adjunct to oral iron supplementation rather than a standalone intervention. These findings should be interpreted with caution due to potential biases and the inclusion of only Chinese children.