TY - JOUR
T1 - Gut microbiome contributions to altered metabolism in a pig model of undernutrition
AU - Chang, Hao Wei
AU - McNulty, Nathan P.
AU - Hibberd, Matthew C.
AU - O’Donnell, David
AU - Cheng, Jiye
AU - Lombard, Vincent
AU - Henrissat, Bernard
AU - Ilkayeva, Olga
AU - Muehlbauer, Michael J.
AU - Newgard, Christopher B.
AU - Barratt, Michael J.
AU - Lin, Xi
AU - Odle, Jack
AU - Gordon, Jeffrey I.
N1 - Funding Information:
Author contributions: H.-W.C., N.P.M., M.J.B., X.L., J.O., and J.I.G. designed research; H.-W.C., N.P.M., D.O., J.C., O.I., M.J.M., X.L., and J.O. performed research; H.-W.C., M.C.H., J.C., V.L., B.H., C.B.N., and J.I.G. analyzed data; and H.-W.C. and J.I.G. wrote the paper. Reviewers: E.E., Weizmann Institute of Science; and D.A.R., Stanford University School of Medicine. Competing interest statement: J.I.G. is a cofounder and N.P.M. is an employee of Matatu, Inc., a company characterizing the role of microbiota development and diet-by-microbiome interactions in animal health. This study received no funding from Matatu, Inc. No experimental or computational methods or datasets arising from this project were provided to Matatu, Inc., nor was any intellectual property belonging to Matatu, Inc. used in these studies. H-W.C., M.C.H., D.O., J.C., V.L., B.H., O.I., M.J.M., C.B.N., and M.J.B. are not affiliated with and do not receive financial support from Matatu. J.O. has conducted experimental animal trials for Matatu under research service agreements with his University (NCSU). This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). 1Present address: Matatu, Inc., St. Louis, MO 63110. 2To whom correspondence may be addressed. Email: jgordon@wustl.edu. This article contains supporting information online at https://www.pnas.org/lookup/suppl/ doi:10.1073/pnas.2024446118/-/DCSupplemental. Published May 17, 2021.
Funding Information:
ACKNOWLEDGMENTS. We thank Maria Karlsson, Marty Meier, Sabrina Wagoner, Justin Serugo, Su Deng, Jessica Hoisington-López, Kaitlyn Walker, Kaylyn Goranson, and Andrew Smith for superb technical assistance and Arjun Raman and Zachary Beller for helpful discussions during development of EMMER (entropy-based method for microbial ecology research). This work was supported by NIH Grant DK30292 (to J.I.G.) and the Bill & Melinda Gates Foundation (X.L.). H-W C. is the recipient of a “Government Scholarship to Study Abroad Predoctoral Fellowship, Taiwan.” J.I.G. is the recipient of a Thought Leader award from Agilent Technologies.
Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/5/25
Y1 - 2021/5/25
N2 - The concept that gut microbiome-expressed functions regulate ponderal growth has important implications for infant and child health, as well as animal health. Using an intergenerational pig model of diet restriction (DR) that produces reduced weight gain, we developed a feature-selection algorithm to identify representative characteristics distinguishing DR fecal microbiomes from those of full-fed (FF) pigs as both groups consumed a common sequence of diets during their growth cycle. Gnotobiotic mice were then colonized with DR and FF microbiomes and subjected to controlled feeding with a pig diet. DR microbiomes have reduced representation of genes that degrade dominant components of late growth-phase diets, exhibit reduced production of butyrate, a key host-accessible energy source, and are causally linked to reduced hepatic fatty acid metabolism (β-oxidation) and the selection of alternative energy substrates. The approach described could aid in the development of guidelines for microbiome stewardship in diverse species, including farm animals, in order to support their healthy growth.
AB - The concept that gut microbiome-expressed functions regulate ponderal growth has important implications for infant and child health, as well as animal health. Using an intergenerational pig model of diet restriction (DR) that produces reduced weight gain, we developed a feature-selection algorithm to identify representative characteristics distinguishing DR fecal microbiomes from those of full-fed (FF) pigs as both groups consumed a common sequence of diets during their growth cycle. Gnotobiotic mice were then colonized with DR and FF microbiomes and subjected to controlled feeding with a pig diet. DR microbiomes have reduced representation of genes that degrade dominant components of late growth-phase diets, exhibit reduced production of butyrate, a key host-accessible energy source, and are causally linked to reduced hepatic fatty acid metabolism (β-oxidation) and the selection of alternative energy substrates. The approach described could aid in the development of guidelines for microbiome stewardship in diverse species, including farm animals, in order to support their healthy growth.
KW - Gut microbiome
KW - carbohydrate-active enzymes
KW - feature selection/information theory
KW - malnutrition
KW - metabolic regulation
UR - http://www.scopus.com/inward/record.url?scp=85106373065&partnerID=8YFLogxK
U2 - 10.1073/pnas.2024446118
DO - 10.1073/pnas.2024446118
M3 - Article
C2 - 34001614
AN - SCOPUS:85106373065
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
M1 - e2024446118
ER -