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

196 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

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10.1126/science.aba3683

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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

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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",

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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

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AU - Yoo, Woongjae

AU - Zieba, Jacob K.

AU - Foegeding, Nora J.

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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.

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

Abstract

Bibliographical note

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