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Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial
Open accessAbstract
Objective Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. Design We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. Results Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (p interaction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. Conclusion Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. Trial registration number NCT00072995 .
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“Changes in TMAO and choline associated with increased insulin sensitivity in a weight-loss intervention study of obese individuals.155”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [155]
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Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,772
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762
Self-citationLinking long-term dietary patterns with gut microbial enterotypes
Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y.-Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., et al. (2011) · Science · doi:10.1126/science.1208344 · Cited by 6,513
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Self-citationRichness of human gut microbiome correlates with metabolic markers
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Self-citationIntestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400
Human gut microbes impact host serum metabolome and insulin sensitivity
Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A. H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., et al. (2016) · Nature · doi:10.1038/nature18646 · Cited by 2,116
Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates
Sacks, F. M., Bray, G. A., Carey, V. J., Smith, S. R., Ryan, D. H., Anton, S. D., McManus, K., Champagne, C. M., Bishop, L. M., Laranjo, N., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0804748 · Cited by 1,966
Self-citationGut microbiome and serum metabolome alterations in obesity and after weight-loss intervention
Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., et al. (2017) · Nature Medicine · doi:10.1038/nm.4358 · Cited by 1,501
Self-citationA gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., Le, A., Cowan, T. M., Nolan, G. P., Fischbach, M. A., et al. (2017) · Nature · doi:10.1038/nature24661 · Cited by 1,425
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070
Dumas, M.-E., Barton, R. H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., Fearnside, J., Tatoud, R., Blanc, V., Lindon, J. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601056103 · Cited by 1,042
Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis
Guasch‐Ferré, M., Hruby, A., Toledo, E., Clish, C. B., Martínez‐González, M. Á., Salas‐Salvadó, J., & Hu, F. B. (2016) · Diabetes Care · doi:10.2337/dc15-2251 · Cited by 916
de la Cuesta-Zuluaga, J., Mueller, N. T., Corrales-Agudelo, V., Velásquez-Mejía, E. P., Carmona, J. A., Abad, J. M., & Escobar, J. S. (2017) · Diabetes Care · doi:10.2337/dc16-1324 · Cited by 704
Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults
Würtz, P., Soininen, P., Kangas, A. J., Rönnemaa, T., Lehtimäki, T. J., Kähönen, M. A. P., Viikari, J. S. A., Raitakari, O. T., & Ala‐Korpela, M. (2012) · Diabetes Care · doi:10.2337/dc12-0895 · Cited by 562
Wang, Z., Tang, W. H. W., Buffa, J. A., Fu, X., Britt, E. B., Koeth, R. A., Levison, B. S., Fan, Y., Wu, Y., & Hazen, S. L. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu002 · Cited by 559
γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L-Carnitine to TMAO
Koeth, R. A., Levison, B. S., Culley, M. K., Buffa, J. A., Wang, Z., Gregory, J. C., Org, E., Wu, Y., Li, L., Smith, J. D., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.006 · Cited by 546
Self-citationHeianza, Y., Ma, W., Manson, J. E., Rexrode, K. M., & Qi, L. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004947 · Cited by 544
Self-citationInfluence of high-fat diet on gut microbiota
Murphy, E. A., Velázquez, K. T., & Herbert, K. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000209 · Cited by 510
Fava, F., Gitau, R., Griffin, B. A., Gibson, G. R., Tuohy, K. M., & Lovegrove, J. A. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.33 · Cited by 440
Gu, Y., Wang, X., Li, J., Zhang, Y., Zhong, H., Liu, R., Zhang, D., Feng, Q., Xie, X., Hong, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01682-2 · Cited by 402
Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota
Zhu, Y., Jameson, E., Crosatti, M., Schäfer, H., Rajakumar, K., Bugg, T. D. H., & Chen, Y. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316569111 · Cited by 372
Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis
Miao, J., Ling, A. V., Manthena, P. V., Gearing, M. E., Graham, M. J., Crooke, R. M., Croce, K. J., Esquejo, R. M., Clish, C. B., Morbid Obesity Study Group, et al. (2015) · Nature Communications · doi:10.1038/ncomms7498 · Cited by 368
Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet
Gao, X., Liu, X., Xu, J., Xue, C., Xue, Y., & Wang, Y. (2014) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2014.03.001 · Cited by 360
Fennema, D., Phillips, I. R., & Shephard, E. A. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.070615 · Cited by 355
Org, E., Blum, Y., Kasela, S., Mehrabian, M., Kuusisto, J., Kangas, A. J., Soininen, P., Wang, Z., Ala‐Korpela, M., Hazen, S. L., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1194-2 · Cited by 337
Shih, D. M., Wang, Z., Lee, R., Meng, Y., Che, N., Charugundla, S., Qi, H., Wu, J., Pan, C., Brown, J. M., et al. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m051680 · Cited by 335
Schugar, R. C., Shih, D. M., Warrier, M., Helsley, R. N., Burrows, A., Ferguson, D., Brown, A. L., Gromovsky, A. D., Heine, M., Chatterjee, A., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.077 · Cited by 291
Self-citationThe Role of Gut Microbiota on Insulin Resistance
Caricilli, A. M., & Saad, M. A. (2013) · Nutrients · doi:10.3390/nu5030829 · Cited by 285
Islet α cells and glucagon--critical regulators of energy homeostasis
Campbell, J. E., & Drucker, D. J. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.51 · Cited by 266
Miller, C. A., Corbin, K. D., da Costa, K.-A., Zhang, S., Zhao, X., Galanko, J. A., Blevins, T., Bennett, B. J., O’Connor, A., & Zeisel, S. H. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.087692 · Cited by 240
Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels
Dambrova, M., Latkovskis, G., Kuka, J., Strele, I., Konrade, I., Grinberga, S., Hartmane, D., Pugovics, O., Erglis, A., & Liepinsh, E. (2016) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0035-1569330 · Cited by 229
Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes
Shan, Z., Sun, T., Huang, H., Chen, S., Chen, L., Luo, C., Yang, W., Yang, X., Yao, P., Cheng, J., et al. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.157107 · Cited by 210
Circulating Metabolite Predictors of Glycemia in Middle-Aged Men and Women
Würtz, P., Tiainen, M., Mäkinen, V., Kangas, A. J., Soininen, P., Saltevo, J. T., Keinanen-Kiukaanniemi, S. M., Mäntyselkä, P. T., Lehtimäki, T. J., Laakso, M., et al. (2012) · Diabetes Care · doi:10.2337/dc11-1838 · Cited by 206
Raubenheimer, P. J., Nyirenda, M., & Walker, B. R. (2006) · Diabetes · doi:10.2337/db06-0097 · Cited by 199
Rohrmann, S., Linseisen, J., Allenspach, M., von Eckardstein, A., & Müller, D. (2016) · The Journal of Nutrition · doi:10.3945/jn.115.220103 · Cited by 197
Lim, J., Savchenkov, A. A., Dale, E., Liang, W. G., Eliyahu, D., Ilchenko, V. S., Matsko, A. B., Maleki, L., & Wong, C. W. (2017) · RePEc: Research Papers in Economics · Cited by 152
Zhang, X., Wang, Y., Hao, F., Zhou, X., Han, X., Tang, H., & Ji, L. (2009) · Journal of Proteome Research · doi:10.1021/pr900524z · Cited by 147
Probiotic supplementation and trimethylamine‐N‐oxide production following a high‐fat diet
Boutagy, N. E., Neilson, A. P., Osterberg, K. L., Smithson, A. T., Englund, T. R., Davy, B. M., Hulver, M. W., & Davy, K. P. (2015) · Obesity · doi:10.1002/oby.21212 · Cited by 127
Obeid, R., Awwad, H. M., Rabagny, Y., Graeber, S., Herrmann, W., & Geisel, J. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.121269 · Cited by 117
Dumas, M.-E., Rothwell, A. R., Hoyles, L., Aranias, T., Chilloux, J., Calderari, S., Noll, E. M., Péan, N., Boulangé, C. L., Blancher, C., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.039 · Cited by 114
Short-term high-fat diet increases postprandial trimethylamine- N -oxide in humans
Boutagy, N. E., Neilson, A. P., Osterberg, K. L., Smithson, A. T., Englund, T. R., Davy, B. M., Hulver, M. W., & Davy, K. P. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.07.002 · Cited by 102
Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials
Zheng, Y., Ceglarek, U., Huang, T., Li, L., Rood, J. C., Ryan, D. H., Bray, G. A., Sacks, F. M., Schwarzfuchs, D., Thiery, J., et al. (2016) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.117689 · Cited by 89
Self-citationMetabolic Effects of L-carnitine on Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Vidal‐Casariego, A., Peláez, R. B., Faedo, C. M., Calvo-Gracia, F., Valero-Zanuy, M. Á., Pérez, L. M. L., & Compés, C. C. (2013) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0033-1333688 · Cited by 85
Heianza, Y., Sun, D., Smith, S. R., Bray, G. A., Sacks, F. M., & Qi, L. (2018) · Diabetes Care · doi:10.2337/dc17-2108 · Cited by 81
Self-citationPrevention of type 2 diabetes in obese at-risk subjects: a systematic review and meta-analysis
Merlotti, C., Morabito, A., Ceriani, V., & Pontiroli, A. E. (2014) · Acta Diabetologica · doi:10.1007/s00592-014-0624-9 · Cited by 58
Flavin-containing monooxygenase 3 and human disease
Motika, M. S., Zhang, J., & Cashman, J. R. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.3.6.831 · Cited by 53
Malinowska, A. M., Szwengiel, A., & Chmurzyńska, A. (2016) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2016.1256379 · Cited by 47
Zheng, Y., Ceglarek, U., Huang, T., Wang, T., Heianza, Y., Ma, W., Bray, G. A., Thiery, J., Sacks, F. M., & Qi, L. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1760 · Cited by 33
Self-citationSilvestre, M. P., Goode, J. P., Vlaskovsky, P., McMahon, C., Tay, A., & Poppitt, S. D. (2017) · Obesity Reviews · doi:10.1111/obr.12631 · Cited by 17
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Metadata
- Authors
- Heianza, Y., Sun, D., Li, X., DiDonato, J. A., Bray, G. A., Sacks, F. M., & Qi, L.
- Affiliations
- Tulane University (US)
- Cleveland Clinic (US)
- Pennington Biomedical Research Center (US)
- Harvard University (US)
- Corresponding author
- Qi, Lu
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2018-06-02
- Volume
- 68
- Issue
- 2
- Pages
- 263-270
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC6275143
- OpenAlex
- W2806227292
- Cited by
- 177
- References
- 52
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 22 · 2023: 22 · 2022: 25 · 2021: 32 · 2020: 18 · 2019: 16 · 2018: 6
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- Japan Society for the Promotion of Science
- United States-Israel Binational Science Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases
- Boston Obesity Nutrition Research Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- gut microbiota metabolites, trimethylamine N-oxide, choline, L-carnitine, insulin resistance, insulin sensitivity, glucose metabolism, weight loss diet, macronutrient composition, dietary fat intake, branched-chain amino acids, aromatic amino acids, obesity, POUNDS Lost trial
- MeSH terms
- Gastrointestinal Microbiome, Adult, Amino Acids, Carnitine, Choline, Diet, Reducing, Female, Glucose, Humans, Insulin Resistance, Male, Massachusetts, Methylamines, Obesity, Overweight
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