Bifidobacterium longum and microbiome maturation modify a nutrient intervention for stunting in Zimbabwean infants

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BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS), which has been widely tested to reduce child stunting, has largely modest effects to date, but the mechanisms underlying these modest effects are unclear. Child stunting is a longstanding indicator of chronic undernutrition and it remains a prevalent public health problem. The infant gut microbiome may be a key contributor to stunting; and mother and infant fucosyltransferase (FUT) phenotypes are important determinants of infant microbiome composition. METHODS: We investigated whether mother-infant FUT status (n = 792) and infant gut microbiome composition (n = 354 fecal specimens from 172 infants) modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in secondary analysis of a randomized trial in rural Zimbabwe. FINDINGS: We found that the impact of the IYCF intervention on stunting was modified by: (i) mother-infant FUT2+/FUT3- phenotype (difference-in-differences -32.6% [95% CI: -55.3%, -9.9%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences -68.1% [95% CI: -99.0%, -28.5%); and (iii) greater relative abundance of B. longum (differences-in-differences 49.1% [95% CI: 26.6%, 73.6%]). The dominant strains of B. longum when the intervention started were most similar to the proficient milk oligosaccharide utilizer subspecies infantis, which decreased with infant age and differed by mother-infant FUT2+/FUT3- phenotypes. INTERPRETATION: These findings indicate that a persistently "younger" microbiome at initiation of the intervention reduced its benefits on stunting in areas with a high prevalence of growth restriction. FUNDING: Bill and Melinda Gates Foundation, UK DFID/Aid, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, UNICEF, and Nutricia Research Foundation.

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