학술논문
Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition.
Document Type
article
Author
Chang, Hao-Wei; Lee, Evan; Wang, Yi; Zhou, Cyrus; Pruss, Kali; Henrissat, Suzanne; Chen, Robert; Kao, Clara; Hibberd, Matthew; Lynn, Hannah; Webber, Daniel; Crane, Marie; Cheng, Jiye; Rodionov, Dmitry; Arzamasov, Aleksandr; Castillo, Juan; Couture, Garret; Chen, Ye; Balcazo, Nikita; Terrapon, Nicolas; Henrissat, Bernard; Ilkayeva, Olga; Muehlbauer, Michael; Newgard, Christopher; Mostafa, Ishita; Das, Subhasish; Mahfuz, Mustafa; Osterman, Andrei; Barratt, Michael; Ahmed, Tahmeed; Gordon, Jeffrey; Lebrilla, Carlito
Source
Nature Microbiology. 9(4)
Subject
Language
Abstract
Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.