High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide

Woongjae Yoo; Jacob K. Zieba; Nora J. Foegeding; Teresa P. Torres; Catherine D. Shelton; Nicolas G. Shealy; Austin J. Byndloss; Stephanie A. Cevallos; Erik Gertz; Connor R. Tiffany; Julia D. Thomas; Yael Litvak; Henry Nguyen; Erin E. Olsan; Brian J. Bennett; Jeffrey C. Rathmell; Amy S. Major; Andreas J. Bäumler; Mariana X. Byndloss

doi:10.1126/science.aba3683

High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide

Woongjae Yoo
, Jacob K. Zieba
, Nora J. Foegeding
, Teresa P. Torres
, Catherine D. Shelton
, Nicolas G. Shealy
, Austin J. Byndloss
, Stephanie A. Cevallos
, Erik Gertz
, Connor R. Tiffany
, Julia D. Thomas
, Yael Litvak
, Henry Nguyen
, Erin E. Olsan
, Brian J. Bennett
, Jeffrey C. Rathmell
, Amy S. Major
, Andreas J. Bäumler^*
, Mariana X. Byndloss^*

^*Corresponding author for this work

Department of Biological Chemistry

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

267 Scopus citations

Abstract

A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli. In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.

Original language	English
Pages (from-to)	813-818
Number of pages	6
Journal	Science
Volume	373
Issue number	6556
DOIs	https://doi.org/10.1126/science.aba3683
State	Published - 13 Aug 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1126/science.aba3683

Cite this

Yoo, W., Zieba, J. K., Foegeding, N. J., Torres, T. P., Shelton, C. D., Shealy, N. G., Byndloss, A. J., Cevallos, S. A., Gertz, E., Tiffany, C. R., Thomas, J. D., Litvak, Y., Nguyen, H., Olsan, E. E., Bennett, B. J., Rathmell, J. C., Major, A. S., Bäumler, A. J., & Byndloss, M. X. (2021). High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science, 373(6556), 813-818. https://doi.org/10.1126/science.aba3683

@article{a1c201dce1e0437e821dac6cc89abf59,

title = "High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide",

abstract = "A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli. In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.",

author = "Woongjae Yoo and Zieba, \{Jacob K.\} and Foegeding, \{Nora J.\} and Torres, \{Teresa P.\} and Shelton, \{Catherine D.\} and Shealy, \{Nicolas G.\} and Byndloss, \{Austin J.\} and Cevallos, \{Stephanie A.\} and Erik Gertz and Tiffany, \{Connor R.\} and Thomas, \{Julia D.\} and Yael Litvak and Henry Nguyen and Olsan, \{Erin E.\} and Bennett, \{Brian J.\} and Rathmell, \{Jeffrey C.\} and Major, \{Amy S.\} and B{\"a}umler, \{Andreas J.\} and Byndloss, \{Mariana X.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",

year = "2021",

month = aug,

day = "13",

doi = "10.1126/science.aba3683",

language = "אנגלית",

volume = "373",

pages = "813--818",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6556",

}

Yoo, W, Zieba, JK, Foegeding, NJ, Torres, TP, Shelton, CD, Shealy, NG, Byndloss, AJ, Cevallos, SA, Gertz, E, Tiffany, CR, Thomas, JD, Litvak, Y, Nguyen, H, Olsan, EE, Bennett, BJ, Rathmell, JC, Major, AS, Bäumler, AJ & Byndloss, MX 2021, 'High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide', Science, vol. 373, no. 6556, pp. 813-818. https://doi.org/10.1126/science.aba3683

TY - JOUR

T1 - High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide

AU - Yoo, Woongjae

AU - Zieba, Jacob K.

AU - Foegeding, Nora J.

AU - Torres, Teresa P.

AU - Shelton, Catherine D.

AU - Shealy, Nicolas G.

AU - Byndloss, Austin J.

AU - Cevallos, Stephanie A.

AU - Gertz, Erik

AU - Tiffany, Connor R.

AU - Thomas, Julia D.

AU - Litvak, Yael

AU - Nguyen, Henry

AU - Olsan, Erin E.

AU - Bennett, Brian J.

AU - Rathmell, Jeffrey C.

AU - Major, Amy S.

AU - Bäumler, Andreas J.

AU - Byndloss, Mariana X.

PY - 2021/8/13

Y1 - 2021/8/13

N2 - A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli. In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.

AB - A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli. In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.

UR - https://www.scopus.com/pages/publications/85112423896

U2 - 10.1126/science.aba3683

DO - 10.1126/science.aba3683

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 34385401

AN - SCOPUS:85112423896

SN - 0036-8075

VL - 373

SP - 813

EP - 818

JO - Science

JF - Science

IS - 6556

ER -

High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this