Synergistic Effects of Standardized Moringa oleifera Leaf Extract and a Probiotic Consortium on Intestinal Permeability and Environmental Enteric Dysfunction Biomarkers in Indonesian Children: A Randomized Controlled Trial

Abstract

Background: Environmental enteric dysfunction (EED) underlies much of the residual stunting and anemia that persist in Indonesian children despite nutrition programs. Moringa oleifera Lam. (Moringaceae) leaves contain quercetin, kaempferol, chlorogenic acid, β-sitosterol and glucomoringin-derived isothiocyanates that reinforce tight junctions and dampen mucosal NF-κB signaling, whereas Lactobacillus and Bifidobacterium probiotics generate short-chain fatty acids and displace enteropathogens.

Objective: To determine whether standardized M. oleifera leaf extract co-administered with a defined probiotic consortium reduces intestinal permeability and EED biomarkers in Indonesian children aged 12–59 months.

Methods: In a three-arm, double-blind, placebo-controlled randomized trial, 150 children aged 12–59 months with biomarker-confirmed EED received, for 12 weeks, either standardized 50% ethanolic M. oleifera leaf extract 500 mg/day plus a probiotic consortium of Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus plantarum Dad-13 (1×10¹⁰ CFU/day) [Moringa + Probiotic], M. oleifera plus placebo probiotic [Moringa alone], or double placebo [Placebo]. The primary outcome was the change in the urinary lactulose-to-mannitol (L:M) ratio at week 12.

Results: In intention-to-treat analysis the L:M ratio fell from 0.42 ± 0.09 to 0.18 ± 0.06 with Moringa + Probiotic, from 0.41 ± 0.10 to 0.27 ± 0.08 with Moringa alone and from 0.43 ± 0.09 to 0.39 ± 0.10 with placebo (p < 0.001; d = 1.42 for Moringa + Probiotic versus placebo). EED remission occurred in 62.0%, 36.0% and 18.0% of recipients, respectively (OR 4.82, 95% CI 2.31–10.06, p < 0.001). Fecal myeloperoxidase, alpha-1-antitrypsin and neopterin, serum zonulin, lipopolysaccharide-binding protein and hs-CRP, hemoglobin and height-for-age Z-score all improved more with the combination, and adverse events were comparable across arms.

Conclusion: Co-administration of standardized M. oleifera leaf extract with a multi-strain probiotic consortium restored intestinal barrier function and suppressed EED biomarkers in Indonesian children, supporting a scalable herbal–microbial complementary therapy.