Gut microbiome and environmental enteric dysfunction are unchanged by 18 months of small-quantity lipid-based...

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to improve growth, development and survival among young children in low-resource settings. One hypothesised pathway is through improvements in intestinal health, including modulation of the gut microbiome and reductions in environmental enteric dysfunction (EED). This study examined the effects of SQ-LNS on the gut microbiome and markers of EED and systemic inflammation among young children in Lusaka, Zambia. We conducted intention-to-treat analyses of 302 children aged 27-35 months in a 2 × 2 cluster-randomised trial. Serum biomarkers of EED (soluble CD14, intestinal fatty acid-binding protein) and inflammation (α-1-acid glycoprotein and C-reactive protein) were assessed in 240 children via the Micronutrient and Environmental Enteric Dysfunction Assessment Tool. Differences by SQ-LNS assignment were assessed using unadjusted and adjusted ordinary least squares regression models. Rectal swab samples from 299 children underwent 16S rRNA gene sequencing. Taxonomic profiles were visualised using stacked bar plots, alpha diversity was quantified using Shannon diversity indices and beta diversity was assessed using non-metric multidimensional scaling based on Bray-Curtis dissimilarity matrices. We found that SQ-LNS had no significant effect on EED or inflammation biomarkers and was not associated with differences in gut microbiome α diversity, beta diversity or overall microbial community composition. In exploratory analyses, Enterococcus abundance was lower among children receiving SQ-LNS. Overall, 18 months of SQ-LNS supplementation was not associated with broad changes in intestinal health among young Lusakan children. These findings suggest that the benefits of SQ-LNS operate through pathways other than intestinal health, such as improved nutrient availability.