Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition

Hao Wei Chang; Evan M. Lee; Yi Wang; Cyrus Zhou; Kali M. Pruss; Suzanne Henrissat; Robert Y. Chen; Clara Kao; Matthew C. Hibberd; Hannah M. Lynn; Daniel Webber; Marie Crane; Jiye Cheng; Dmitry A. Rodionov; Aleksandr A. Arzamasov; Juan J. Castillo; Garret Couture; Ye Chen; Nikita P. Balcazo; Carlito B. Lebrilla; Nicolas Terrapon; Bernard Henrissat; Olga Ilkayeva; Michael J. Muehlbauer; Christopher B. Newgard; Ishita Mostafa; Subhasish Das; Mustafa Mahfuz; Andrei L. Osterman; Michael J. Barratt; Tahmeed Ahmed; Jeffrey I. Gordon

doi:10.1038/s41564-024-01628-7

Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition

Hao Wei Chang, Evan M. Lee, Yi Wang, Cyrus Zhou, Kali M. Pruss, Suzanne Henrissat, Robert Y. Chen, Clara Kao, Matthew C. Hibberd, Hannah M. Lynn, Daniel Webber, Marie Crane, Jiye Cheng, Dmitry A. Rodionov, Aleksandr A. Arzamasov, Juan J. Castillo, Garret Couture, Ye Chen, Nikita P. Balcazo, Carlito B. LebrillaNicolas Terrapon, Bernard Henrissat, Olga Ilkayeva, Michael J. Muehlbauer, Christopher B. Newgard, Ishita Mostafa, Subhasish Das, Mustafa Mahfuz, Andrei L. Osterman, Michael J. Barratt, Tahmeed Ahmed, Jeffrey I. Gordon

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Journal	Nature microbiology
DOIs	https://doi.org/10.1038/s41564-024-01628-7
State	Accepted/In press - 2024

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Chang, H. W., Lee, E. M., Wang, Y., Zhou, C., Pruss, K. M., Henrissat, S., Chen, R. Y., Kao, C., Hibberd, M. C., Lynn, H. M., Webber, D., Crane, M., Cheng, J., Rodionov, D. A., Arzamasov, A. A., Castillo, J. J., Couture, G., Chen, Y., Balcazo, N. P., ... Gordon, J. I. (Accepted/In press). Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition. Nature microbiology. https://doi.org/10.1038/s41564-024-01628-7

@article{c586723d272c41d3b03fef4cf7464593,

title = "Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition",

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.",

author = "Chang, {Hao Wei} and Lee, {Evan M.} and Yi Wang and Cyrus Zhou and Pruss, {Kali M.} and Suzanne Henrissat and Chen, {Robert Y.} and Clara Kao and Hibberd, {Matthew C.} and Lynn, {Hannah M.} and Daniel Webber and Marie Crane and Jiye Cheng and Rodionov, {Dmitry A.} and Arzamasov, {Aleksandr A.} and Castillo, {Juan J.} and Garret Couture and Ye Chen and Balcazo, {Nikita P.} and Lebrilla, {Carlito B.} and Nicolas Terrapon and Bernard Henrissat and Olga Ilkayeva and Muehlbauer, {Michael J.} and Newgard, {Christopher B.} and Ishita Mostafa and Subhasish Das and Mustafa Mahfuz and Osterman, {Andrei L.} and Barratt, {Michael J.} and Tahmeed Ahmed and Gordon, {Jeffrey I.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41564-024-01628-7",

language = "English",

journal = "Nature microbiology",

issn = "2058-5276",

}

Chang, HW, Lee, EM, Wang, Y, Zhou, C, Pruss, KM, Henrissat, S, Chen, RY, Kao, C, Hibberd, MC, Lynn, HM, Webber, D, Crane, M, Cheng, J, Rodionov, DA, Arzamasov, AA, Castillo, JJ, Couture, G, Chen, Y, Balcazo, NP, Lebrilla, CB, Terrapon, N, Henrissat, B, Ilkayeva, O, Muehlbauer, MJ, Newgard, CB, Mostafa, I, Das, S, Mahfuz, M, Osterman, AL, Barratt, MJ, Ahmed, T & Gordon, JI 2024, 'Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition', Nature microbiology. https://doi.org/10.1038/s41564-024-01628-7

TY - JOUR

T1 - Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition

AU - Chang, Hao Wei

AU - Lee, Evan M.

AU - Wang, Yi

AU - Zhou, Cyrus

AU - Pruss, Kali M.

AU - Henrissat, Suzanne

AU - Chen, Robert Y.

AU - Kao, Clara

AU - Hibberd, Matthew C.

AU - Lynn, Hannah M.

AU - Webber, Daniel

AU - Crane, Marie

AU - Cheng, Jiye

AU - Rodionov, Dmitry A.

AU - Arzamasov, Aleksandr A.

AU - Castillo, Juan J.

AU - Couture, Garret

AU - Chen, Ye

AU - Balcazo, Nikita P.

AU - Lebrilla, Carlito B.

AU - Terrapon, Nicolas

AU - Henrissat, Bernard

AU - Ilkayeva, Olga

AU - Muehlbauer, Michael J.

AU - Newgard, Christopher B.

AU - Mostafa, Ishita

AU - Das, Subhasish

AU - Mahfuz, Mustafa

AU - Osterman, Andrei L.

AU - Barratt, Michael J.

AU - Ahmed, Tahmeed

AU - Gordon, Jeffrey I.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85188097987&partnerID=8YFLogxK

U2 - 10.1038/s41564-024-01628-7

DO - 10.1038/s41564-024-01628-7

M3 - Article

C2 - 38503977

AN - SCOPUS:85188097987

SN - 2058-5276

JO - Nature microbiology

JF - Nature microbiology

ER -

Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition

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