(P24-027-24) Bifidobacterium longum Strains Modify a Nutrient Intervention for Stunting in Zimbabwean Infants

Objectives: Child stunting is a longstanding indicator of chronic undernutrition. However, it remains a prevalent public health problem. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been widely tested to reduce stunting, but have largely had modest effects. 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. We investigated whether mother-infant FUT status and infant gut microbiome composition modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in the SHINE Trial in Zimbabwe.

Methods: Saliva specimens collected from 792 HIV-uninfected mothers and their infants were used to ascertain FUT2 and 3 phenotypes. 354 fecal specimens from 172 of these infants underwent whole genome sequencing to characterize the microbiome. Bacterial species β-diversity was analyzed using constrained principal coordinates analyses. Interactions between IYCF and (i) paired mother-infant FUT2 and 3 phenotypes and (ii) microbiome composition were investigated using multivariable regression methods. Microbiome bacterial strains were profiled using PanPhlan3.0.

Results: We found that the following features were associated with modified IYCF impact on stunting at 18mo: (i) mother-infant FUT2+/FUT3- phenotype (difference-in-differences -33.0%[95%CI: -55.0%,-10.0%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences -76.0%[95%CI: -99.0%,-32.0%); and (iii) greater relative abundance of B. longum (differences-in-differences 50.0%[95%CI: 26.0%,74.0%]). The dominant strains of B. longum when IYCF 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.

Conclusions: Our findings suggest that a persistently “younger” microbiome, characterized by a high abundance of B. longum and carriage of B. longum strains best suited to breastfeeding, when complementary foods are introduced, may reduce the beneficial effects of an intervention that includes SQ-LNS on infant stunting.

Funding Sources: BMGF, UK DFID, Wellcome Trust, US NIH, UNICEF, Nutricia Research Foundation