Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery

The impact of the gut microbiota on human health: an integrative view

Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710 · see citing works

Intestinal 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 3,402 · see citing works

Mechanisms underlying the resistance to diet-induced obesity in germ-free mice

Bäckhed, F., Manchester, J. K., Semenkovich, C. F., & Gordon, J. I. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605374104 · Cited by 2,615 · see citing works

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435 · see citing works

Intestinal inflammation targets cancer-inducing activity of the microbiota

Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J., Campbell, B. J., Abujamel, T., Dogan, B., Rogers, A. B., et al. (2012) · Science · doi:10.1126/science.1224820 · Cited by 2,263 · see citing works

Diet–microbiota interactions as moderators of human metabolism

Sonnenburg, J. L., & Bäckhed, F. (2016) · Nature · doi:10.1038/nature18846 · Cited by 2,257 · see citing works

Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219 · see citing works

Innate immunity and intestinal microbiota in the development of Type 1 diabetes

Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works

Symptomatic atherosclerosis is associated with an altered gut metagenome

Karlsson, F. H., Fåk, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., Bäckhed, F., & Nielsen, J. (2012) · Nature Communications · doi:10.1038/ncomms2266 · Cited by 1,371 · see citing works

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination

Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G. (2011) · Nature · doi:10.1038/nature10554 · Cited by 1,251 · see citing works

Gut Microbiota-Dependent Trimethylamine <i>N</i> -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease

Tang, W. H. W., Wang, Z., Kennedy, D. J., Wu, Y., Buffa, J. A., Agatisa-Boyle, B., Li, X. S., Levison, B. S., & Hazen, S. L. (2015) · Circulation Research · doi:10.1161/circresaha.116.305360 · Cited by 1,223 · see citing works

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

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 · cited 1× · see citing works

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB

Seldin, M. M., Meng, Y., Qi, H., Zhu, W., Wang, Z., Hazen, S. L., Lusis, A. J., & Shih, D. M. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.002767 · Cited by 911 · see citing works

Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- <i>N</i> -Oxide

Romano, K. A., Vivas, E. I., Amador-Noguez, D., & Rey, F. E. (2015) · mBio · doi:10.1128/mbio.02481-14 · Cited by 777 · see citing works

Resveratrol Attenuates Trimethylamine- <i>N</i> -Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota

Chen, M.-L., Yi, L., Zhang, Y., Zhou, X., Ran, L., Yang, J., Zhu, J.-D., Zhang, Q.-Y., & Mi, M.-T. (2016) · mBio · doi:10.1128/mbio.02210-15 · Cited by 754 · cited 3× · see citing works

Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack

Yin, J., Liao, S., He, Y., Wang, S., Xia, G., Liu, F., Zhu, J., You, C., Chen, Q., Zhou, L., et al. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.115.002699 · Cited by 669 · see citing works

Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation

Gregory, J. C., Buffa, J. A., Org, E., Wang, Z., Levison, B. S., Zhu, W., Wagner, M. A., Bennett, B. J., Li, L., DiDonato, J. A., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.618249 · Cited by 486 · see citing works

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

Stubbs, J. R., House, J. A., Ocque, A. J., Zhang, S., Johnson, C., Kimber, C., Schmidt, K., Gupta, A., Wetmore, J. B., Nolin, T. D., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014111063 · Cited by 450 · see citing works

Choline Diet and Its Gut Microbe–Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload–Induced Heart Failure

Organ, C. L., Otsuka, H., Bhushan, S., Wang, Z., Bradley, J., Trivedi, R., Polhemus, D. J., Tang, W. H. W., Wu, Y., Hazen, S. L., et al. (2016) · Circulation: Heart Failure · doi:10.1161/circheartfailure.115.002314 · Cited by 382 · see citing works

Why do some organisms use a urea-methylamine mixture as osmolyte? Thermodynamic compensation of urea and trimethylamine N-oxide interactions with protein

Lin, T.-Y., & Timasheff, S. N. (1994) · Biochemistry · doi:10.1021/bi00208a021 · Cited by 371 · cited 1× · see citing works

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 · see citing works

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Missailidis, C., Hällqvist, J., Qureshi, A. R., Barany, P., Heimbürger, O., Lindholm, B., Stenvinkel, P., & Bergman, P. (2016) · PLOS ONE · doi:10.1371/journal.pone.0141738 · Cited by 338 · see citing works

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

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 · see citing works

Role of the Gut Microbiome in Obstructive Sleep Apnea–Induced Hypertension

Durgan, D. J., Ganesh, B. P., Cope, J. L., Ajami, N. J., Phillips, S. C., Petrosino, J. F., Hollister, E. B., & Bryan, R. M. (2016) · Hypertension · doi:10.1161/hypertensionaha.115.06672 · Cited by 327 · see citing works

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 &amp; Diabetes · doi:10.1055/s-0035-1569330 · Cited by 229 · see citing works

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study

Lever, M., George, P. M., Slow, S., Bellamy, D., Young, J. M., Ho, M., McEntyre, C. J., Elmslie, J. L., Atkinson, W., Molyneux, S. L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114969 · Cited by 223 · see citing works

Trimethylamine-N-Oxide: A Carnitine-Derived Metabolite That Prolongs the Hypertensive Effect of Angiotensin II in Rats

Ufnal, M., Jazwiec, R., Dadlez, M., Drapala, A., Sikora, M., & Skrzypecki, J. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.09.010 · Cited by 205 · see citing works

Plasma Concentrations of Trimethylamine-N-oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population

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 · see citing works

Pharmacologic Targeting of Bacterial β-Glucuronidase Alleviates Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

LoGuidice, A., Wallace, B. D., Bendel, L., Redinbo, M. R., & Boelsterli, U. A. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.191122 · Cited by 197 · see citing works

L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE−/− transgenic mice expressing CETP

Collins, H. L., Drazul-Schrader, D., Sulpizio, A. C., Koster, P. D., Williamson, Y., Adelman, S. J., Owen, K., Sanli, T., & Bellamine, A. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.10.108 · Cited by 189 · see citing works

Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events

Kim, R. B., Morse, B. L., Djurdjev, O., Tang, M., Muirhead, N., Barrett, B., Holmes, D. T., Madore, F., Clase, C. M., Rigatto, C., et al. (2016) · Kidney International · doi:10.1016/j.kint.2016.01.014 · Cited by 179 · see citing works

Dietary phosphatidylcholine and risk of all-cause and cardiovascular-specific mortality among US women and men ,

Zheng, Y., Li, Y., Rimm, E. B., Hu, F. B., Albert, C. M., Rexrode, K. M., Manson, J. E., & Qi, L. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.131771 · Cited by 100 · see citing works

Dietary metabolism, the gut microbiome, and heart failure

Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works

Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential

Roberts, A. B., Gu, X., Buffa, J. A., Hurd, A. G., Wang, Z., Zhu, W., Gupta, N., Skye, S. M., Cody, D. B., Levison, B. S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0128-1 · Cited by 552 · see citing works

Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women

Wang, Z., Bergeron, N., Levison, B. S., Li, X. S., Chiu, S., Jia, X., Koeth, R. A., Li, L., Wu, Y., Tang, W. H. W., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehy799 · Cited by 496 · see citing works

Microbial modulation of cardiovascular disease

Brown, J. M., & Hazen, S. L. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.149 · Cited by 440 · see citing works

Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites

Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., Ussar, S., Altindis, E., Li, N., Bry, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.060 · Cited by 231 · see citing works

Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism

Soto, M., Herzog, C., Pacheco, J. A., Fujisaka, S., Bullock, K., Clish, C. B., & Kahn, C. R. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0086-5 · Cited by 216 · see citing works

Current Concepts, Opportunities, and Challenges of Gut Microbiome-Based Personalized Medicine in Nonalcoholic Fatty Liver Disease

Sharpton, S. R., Schnabl, B., Knight, R., & Loomba, R. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.11.010 · Cited by 194 · see citing works

Gut microbial metabolite TMAO contributes to renal dysfunction in a mouse model of diet-induced obesity

Sun, G., Yin, Z., Liu, N., Bian, X., Yu, R., Su, X., Zhang, B., & Wang, Y. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.09.108 · Cited by 140 · see citing works

Cardiovascular and antiobesity effects of resveratrol mediated through the gut microbiota

Bird, J. K., Raederstorff, D., Weber, P., & Steinert, R. E. (2017) · Advances in Nutrition · doi:10.3945/an.117.016568 · Cited by 136 · see citing works

Impact of probiotics on weight loss, glucose and lipid metabolism in overweight or obese women: A meta-analysis of randomized controlled trials

Cao, N., Zhao, F., Kwok, L.-Y., Wang, H., & Sun, Z. (2024) · Current Research in Food Science · doi:10.1016/j.crfs.2024.100810 · Cited by 24 · see citing works