Hematology · Medical Literature
Efficacy and safety of prebiotics, probiotics, and synbiotics on hemoglobin and anemia in the pediatric population: A systematic review and meta-analysis.
Abstract
To evaluate the efficacy and safety of prebiotics, probiotics, and synbiotics on hemoglobin levels and anemia in the pediatric population. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs). PubMed, Embase, and CENTRAL were searched up to August 2025. We included RCTs assessing prebiotics, probiotics, or synbiotics on hemoglobin or anemia in children. Random-effects meta-analyses were performed, and certainty of evidence was assessed using GRADE and minimal important differences. The protocol was registered in PROSPERO (CRD420251108276). Nineteen RCTs involving 4188 children were included. Compared to placebo or standard care, prebiotics, probiotics, and synbiotics (alone or with iron) showed no important effects on hemoglobin, hematocrit, or ferritin (certainty: high to very low). However, probiotics versus placebo may reduce anemia (1 RCT; RD: --6 per 100; 95% CI: --15 to +6, low certainty). No serious adverse events were reported; observed events were mainly mild gastrointestinal symptoms. Prebiotics, probiotics, and synbiotics do not provide clinically important benefits on hemoglobin or anemia in children, although they appear safe. Larger, high-quality trials in high-risk populations are needed.
Clinical relevance
Microbiome-targeting interventions (prebiotics, probiotics, synbiotics) have generated significant interest as adjuncts to iron therapy in pediatric anemia, given the known role of gut microbiota in iron absorption and the prevalence of iron-deficiency anemia in children globally. This systematic review and meta-analysis of 19 RCTs (n=4,188 children) directly addresses whether these agents confer measurable hematologic benefit, a question increasingly posed by clinicians managing pediatric anemia in both resource-rich and resource-limited settings. The findings are timely given the growing commercial promotion of these supplements for nutritional optimization in children.
Key findings
1. No clinically important effect on hemoglobin levels was demonstrated with prebiotics, probiotics, or synbiotics (alone or combined with iron) versus placebo or standard care; certainty of evidence ranged from high to very low per GRADE assessment. 2. No clinically important effect on hematocrit was observed across included RCTs, consistent with the null hemoglobin findings. 3. No clinically important effect on serum ferritin was detected, suggesting the lack of benefit extends to iron stores, not just circulating hemoglobin. 4. Probiotics versus placebo showed a possible reduction in anemia prevalence in a single RCT (RD: −6 per 100 children; 95% CI: −15 to +6), rated low certainty — the confidence interval crosses the null, precluding definitive conclusions. 5. No serious adverse events were reported across the 19 included RCTs; observed adverse events were predominantly mild gastrointestinal symptoms. 6. The evidence base comprised 19 RCTs with a total of 4,188 pediatric participants; heterogeneity in populations, interventions, and outcomes limits generalizability and contributed to the wide range of evidence certainty ratings.
Practice implications
Clinicians should not routinely recommend prebiotics, probiotics, or synbiotics as adjuncts to iron therapy or as standalone interventions for improving hemoglobin, hematocrit, or ferritin in children, as current high-to-low certainty evidence shows no clinically meaningful hematologic benefit. The safety profile appears acceptable for children who may receive these agents for other indications, with only mild gastrointestinal side effects reported and no serious adverse events across nearly 4,200 participants. Until larger, high-quality RCTs in well-defined high-risk pediatric populations (e.g., preterm infants, children with malabsorptive conditions) are conducted, standard evidence-based anemia management — including dietary counseling and iron supplementation where indicated — should remain the primary therapeutic strategy.