The impact of milk on gut permeability, fecal 16S rRNA gene microbiota profiling, and fecal metabolomics in children with moderate malnutrition in Sierra Leone: A double-blind, randomized controlled trial

Authors: SON, MINSOO - Washington University; LAURY, MARIE - Washington University; STEPHENSON, KEVIN - Washington University; MAY, THADDAEUS - Baylor College Of Medicine; HENDRIXSON, D - University Of Washington; NGEFBAI, AMARA - The Republic Of Sierra Leone; SONG, JONG - Washington University; NASKIDASHVILI, NINO - Washington University; GOO, YOUNG - Washington University; MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2024
Publication Date: 9/21/2024
Citation: Son, M., Laury, M.L., Stephenson, K.B., May, T., Hendrixson, D.T., Ngefbai, A.S., Song, J.H., Naskidashvili, N., Goo, Y.A., Manary, M.J. 2024. The impact of milk on gut permeability, fecal 16S rRNA gene microbiota profiling, and fecal metabolomics in children with moderate malnutrition in Sierra Leone: A double-blind, randomized controlled trial. The American Journal of Clinical Nutrition. 120(5):1114-1124. https://doi.org/10.1016/j.ajcnut.2024.09.018.
DOI: https://doi.org/10.1016/j.ajcnut.2024.09.018

Interpretive Summary: Despite bovine milk being recognized as a beneficial ingredient in the treatment of malnutrition, the components of milk protein and milk carbohydrate needed to be studied to determine effect on intestinal permeability, fecal bacteria species, and fecal metabolites in moderately malnourished children, as these mechanisms could underlie milk's clinical benefits. In a randomized, double-blind, controlled trial among 413 children with wasting in Sierra Leone, researchers provided four different supplementary foods that varied in protein and carbohydrate sources, finding after 4 weeks that abnormal intestinal permeability did not improve with supplementary feeding, fecal bacteria profiles did not differ between dietary groups, but some metabolite differences were observed, with milk protein consumption increasing amino acid and fatty acid metabolite abundance and milk carbohydrate consumption increasing nucleoside and short-chain fatty acid abundance. This research demonstrated that abnormal intestinal permeability does not improve with 4 weeks of supplementary feeding containing milk components, although milk protein consumption increased amino acid and fatty acid metabolite abundance and milk carbohydrate consumption increased nucleoside and short-chain fatty acid abundance, suggesting longer nutritional interventions may be needed to restore normal gut function in malnourished children.

Technical Abstract: Bovine milk is a beneficial ingredient in the treatment of malnutrition. Our objectives were to determine the effect of dietary milk protein and milk carbohydrate on the intestinal permeability, fecal 16S rRNA gene configuration, and fecal metabolomics of children with moderate malnutrition. This was a randomized, double-blind, controlled trial among 413 children with wasting in rural Sierra Leone who received 1 of the following 4 supplementary foods, which differed in sources of protein and carbohydrate: milk protein and milk carbohydrate (MPMC), milk protein and vegetable carbohydrate (MPVC), vegetable protein and milk carbohydrate (VPMC), or a control group consuming entirely vegetable-based food (VPVC). After 4 wk, urine and stool were collected from participants enrolled with mid-upper arm circumference of <12.1 cm. Urine was analyzed for lactulose excretion (%L). Stool samples were subjected to both 16S rRNA gene analysis to assess ß-diversity and untargeted metabolomic abundance. Among the 386 children who completed permeability testing, the mean difference (95% CI) in %L excretion as compared with VPVC was 0.01(-0.05, 0.07) for MPMC, 0.05 (-0.01, 0.11) for MPVC, and 0.01 (-0.05, 0.07) for VPMC. Of the 374 children who provided a stool sample that was analyzed, the beta-diversity among bacterial taxa was similar between dietary groups (P>0.05 for all comparisons). No significant differences between dietary groups were seen among the 20 most abundant bacterial taxa. Among the 5769 unique metabolomic features identified, greater flavonoid levels in VPVC were seen. Abnormal intestinal permeability do not improve with 4 wk of supplementary feeding. Fecal rRNA do not differ with consumption of different diets.