Microbiome-directed interventions for at-risk infants under 6 months of age in low-income countries: A scoping review

Abstract Abstract Background: Infants under six months of age in low‑income countries (LICs) face high morbidity and mortality, driven by prematurity, low birthweight (LBW), malnutrition, infection, and environmental enteric dysfunction. Increasing evidence links these vulnerabilities to disruptions in early gut microbiome development. Microbiome-directed interventions such as prebiotics, probiotics, and synbiotics have been proposed to improve health outcomes, yet evidence for their use in LICs remains unclear. This scoping review maps existing evidence on microbiome‑directed interventions for at‑risk infants under six months in LICs. Methods: Following PRISMA‑ScR guidelines, we searched PubMed, supplemented by reference checking and expert consultation. Eligible studies focused on infants under six months in LICs receiving any microbiome‑directed intervention compared with placebo or standard care. Data were extracted and synthesised narratively across four population groups: preterm infants, wasted infants, term/LBW infants, and healthy infants. Results: Of 7,994 records identified, 13 studies met inclusion criteria across seven countries. Evidence in preterm infants suggests potential reductions in necrotising enterocolitis (NEC), late‑onset sepsis, and time to full enteral feeding, though findings were inconsistent and limited by small sample sizes and heterogeneity in strains, dosing, and outcomes. One small trial in wasted infants demonstrated modest improvements in microbiome composition and short‑term weight gain. Among stable newborns, synbiotic supplementation in one large trial reduced systemic inflammation and improved gut-health biomarkers, while others showed transient or no clinical effects. Conclusions: Evidence for microbiome‑directed interventions in infants in LICs is limited and heterogeneous, though small studies suggest probiotics may reduce NEC, sepsis, and mortality in preterm infants, aligning with evidence from higher‑income settings. Evidence in term/LBW or wasted infants under six months is limited. Among stable newborns, biomarker improvements are encouraging, yet their translation into meaningful clinical outcomes remains unclear. Future research should prioritise well‑powered, placebo‑controlled trials with clearly defined subpopulations, harmonised outcomes, and integration of both biomarker and clinical endpoints.