Prevotella copri -related effects of a therapeutic food for malnutrition.

Autor: Chang HW; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Lee EM; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Wang Y; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Zhou C; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Pruss KM; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Henrissat S; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille University, F-13288, Marseille, France., Chen RY; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Kao C; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Hibberd MC; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Lynn HM; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Webber DM; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Crane M; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Cheng J; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA., Rodionov DA; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA., Arzamasov AA; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA., Castillo JJ; Department of Chemistry, University of California, Davis, CA 95616 USA., Couture G; Department of Chemistry, University of California, Davis, CA 95616 USA., Chen Y; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Chemistry, University of California, Davis, CA 95616 USA., Balcazo NP Jr; Department of Chemistry, University of California, Davis, CA 95616 USA., Lebrilla CB; Department of Chemistry, University of California, Davis, CA 95616 USA., Terrapon N; Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille University, F-13288, Marseille, France., Henrissat B; Department of Biotechnology and Biomedicine (DTU Bioengineering), Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.; Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Ilkayeva O; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710 USA.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710 USA.; Department of Medicine, Duke University Medical Center, Durham, NC, 27710 USA., Muehlbauer MJ; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710 USA.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710 USA., Newgard CB; Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710 USA.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710 USA.; Department of Medicine, Duke University Medical Center, Durham, NC, 27710 USA.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710 USA., Mostafa I; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh., Das S; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh., Mahfuz M; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh., Osterman AL; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA., Barratt MJ; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA., Ahmed T; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh., Gordon JI; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 20. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1101/2023.08.11.553030
Abstrakt: Preclinical and clinical studies are providing evidence that the healthy growth of infants and children reflects, in part, healthy development of their gut microbiomes 1-5 . This process of microbial community assembly and functional maturation is perturbed in children with acute malnutrition. Gnotobiotic animals, colonized with microbial communities from children with severe and moderate acute malnutrition, have been used to develop microbiome-directed complementary food (MDCF) formulations for repairing the microbiomes of these children during the weaning period 5 . Bangladeshi children with moderate acute malnutrition (MAM) participating in a previously reported 3-month-long randomized controlled clinical study of one such formulation, MDCF-2, exhibited significantly improved weight gain compared to a commonly used nutritional intervention despite the lower caloric density of the MDCF 6 . Characterizing the 'metagenome assembled genomes' (MAGs) of bacterial strains present in the microbiomes of study participants revealed a significant correlation between accelerated ponderal growth and the expression by two Prevotella copri MAGs of metabolic pathways involved in processing of MDCF-2 glycans 1 . To provide a direct test of these relationships, we have now performed 'reverse translation' experiments using a gnotobiotic mouse model of mother-to-offspring microbiome transmission. Mice were colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains cultured from Bangladeshi infants/children in the study population, with or without P. copri isolates resembling the MAGs. By combining analyses of microbial community assembly, gene expression and processing of glycan constituents of MDCF-2 with single nucleus RNA-Seq and mass spectrometric analyses of the intestine, we establish a principal role for P. copri in mediating metabolism of MDCF-2 glycans, characterize its interactions with other consortium members including Bifidobacterium longum subsp. infantis , and demonstrate the effects of P. copri -containing consortia in mediating weight gain and modulating the activities of metabolic pathways involved in lipid, amino acid, carbohydrate plus other facets of energy metabolism within epithelial cells positioned at different locations in intestinal crypts and villi. Together, the results provide insights into structure/function relationships between MDCF-2 and members of the gut communities of malnourished children; they also have implications for developing future prebiotic, probiotic and/or synbiotic therapeutics for microbiome restoration in children with already manifest malnutrition, or who are at risk for this pervasive health challenge.
Databáze: MEDLINE