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Effects of microbiota-directed foods in gnotobiotic animals and undernourished children

ABSTRACT: A microbiota-directed complementary food, developed and characterized in gnotobiotic mice and piglets colonized with microbial therapeutic targets, has wide-ranging beneficial effects on biomarkers and mediators of postnatal development in Bangladeshi children with moderate acute malnutrition

PROVIDER: PRJEB26419 | ENA |

REPOSITORIES: ENA

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Comparing the effects of microbiota-directed therapeutic foods in gnotobiotic mice, gnotobiotic piglets and undernourished children

Project description:We illustrate an approach for integrating preclinical gnotobiotic animal models with human studies to understand the contributions of perturbed gut microbiota development to childhood undernutrition, and to identify new microbiota-directed therapeutic concepts/leads. Combining metabolomic and proteomic analyses of serially collected plasma samples with metagenomic analyses of serially collected fecal samples, we characterized the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned to moderate acute malnutrition (MAM) after standard treatment. Gnotobiotic mice were subsequently colonized with a defined consortium of bacterial strains representing different stages of microbiota development in healthy children from Bangladesh. Administering different combinations of Bangladeshi complementary food ingredients to colonized mice and germ-free controls revealed diet-dependent changes in representation and metabolism of targeted weaning-phase strains, including accompanying increases in branched-chain amino acids, plus diet- and colonization-dependent augmentation of IGF-1/mTOR signaling. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes were subsequently examined in gnotobiotic mice colonized with post-SAM MAM microbiota and in gnotobiotic piglets colonized with a defined consortium of targeted age- and growth-discriminatory bacteria. Finally, ar andomized, double-blind study revealed a lead MDCF that affected the representation of targeted bacterial taxa and increased levels of biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function.

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Effects of microbiota-directed foods in gnotobiotic animals and undernourished children.

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Effects of current therapeutic foods in undernourished Bangladeshi children compared to microbiota-directed food prototypes in gnotobiotic mice and piglets

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