Assessment of Dietary Habits, Lifestyle Factors and Circulating Trimethylamine N-oxide Status in Moroccan Colorectal Cancer Patients: A Cross-Sectional Study

Al-Obaide, M. A. I., Singh, R., Datta, P., Rewers-Felkins, K. A., Salguero, M. V., Al-Obaidi, I., Kottapalli, K. R., & Vasylyeva, T. L. (2017). Gut Microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD. Journal of Clinical Medicine, 6(9), E86. https://doi.org/10.3390/jcm6090086 DOI: https://doi.org/10.3390/jcm6090086

American Diabetes Association Professional Practice Committee. (2024). 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes—2024. Diabetes Care, 47(Supplement_1), S20–S42. https://doi.org/10.2337/dc24-S002 DOI: https://doi.org/10.2337/dc24-S002

Argyridou, S., Bernieh, D., Henson, J., Edwardson, C. L., Davies, M. J., Khunti, K., Suzuki, T., & Yates, T. (2020). Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes. BMJ Open Diabetes Research & Care, 8(2), e001359. https://doi.org/10.1136/bmjdrc-2020-001359 DOI: https://doi.org/10.1136/bmjdrc-2020-001359

Bae, S., Ulrich, C. M., Neuhouser, M. L., Malysheva, O., Bailey, L. B., Xiao, L., Brown, E. C., Cushing-Haugen, K. L., Zheng, Y., Cheng, T.-Y. D., Miller, J. W., Green, R., Lane, D. S., Beresford, S. A. A., & Caudill, M. A. (2014). Plasma choline metabolites and colorectal cancer risk in the Women’s Health Initiative Observational Study. Cancer Research, 74(24), 7442–7452. https://doi.org/10.1158/0008-5472.CAN-14-1835 DOI: https://doi.org/10.1158/0008-5472.CAN-14-1835

Benítez-Páez, A., Kjølbæk, L., Gómez Del Pulgar, E. M., Brahe, L. K., Astrup, A., Matysik, S., Schött, H.-F., Krautbauer, S., Liebisch, G., Boberska, J., Claus, S., Rampelli, S., Brigidi, P., Larsen, L. H., & Sanz, Y. (2019). A multi-omics approach to unraveling the microbiome-mediated effects of arabinoxylan oligosaccharides in overweight humans. mSystems, 4(4), e00209-19. https://doi.org/10.1128/mSystems.00209-19 DOI: https://doi.org/10.1128/mSystems.00209-19

Bennett, B. J., de Aguiar Vallim, T. Q., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., Edwards, P. A., Hazen, S. L., & Lusis, A. J. (2013). Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metabolism, 17(1), 49–60. https://doi.org/10.1016/j.cmet.2012.12.011 DOI: https://doi.org/10.1016/j.cmet.2012.12.011

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). Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet: Probiotics, TMAO, and High-Fat Diet. Obesity (Silver Spring, Md.), 23(12), 2357–2363. https://doi.org/10.1002/oby.21212 DOI: https://doi.org/10.1002/oby.21212

Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834 DOI: https://doi.org/10.3322/caac.21834

Budoff, M. J., de Oliveira Otto, M. C., Li, X. S., Lee, Y., Wang, M., Lai, H. T. M., Lemaitre, R. N., Pratt, A., Tang, W. H. W., Psaty, B. M., Siscovick, D. S., Hazen, S. L., & Mozaffarian, D. (2025). Trimethylamine-N-oxide (TMAO) and risk of incident cardiovascular events in the multi ethnic study of Atherosclerosis. Scientific Reports, 15(1), 23362. https://doi.org/10.1038/s41598-025-05903-3 DOI: https://doi.org/10.1038/s41598-025-05903-3

Byrd, D. A., Zouiouich, S., Karwa, S., Li, X. S., Wang, Z., Sampson, J. N., Loftfield, E., Huang, W.-Y., Hazen, S. L., & Sinha, R. (2024). Associations of serum trimethylamine N-oxide and its precursors with colorectal cancer risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort. Cancer, 130(11), 1982–1990. https://doi.org/10.1002/cncr.35219 DOI: https://doi.org/10.1002/cncr.35219

Cheng, E., Hung, S.-C., & Lin, T.-Y. (2025). Association of trimethylamine N-oxide and metabolites with kidney function decline in patients with chronic kidney disease. Clinical Nutrition (Edinburgh, Scotland), 44, 239–247. https://doi.org/10.1016/j.clnu.2024.12.001 DOI: https://doi.org/10.1016/j.clnu.2024.12.001

Cheng, W.-L., Li, S.-J., Lee, T.-I., Lee, T.-W., Chung, C.-C., Kao, Y.-H., & Chen, Y.-J. (2021). Sugar fructose triggers gut dysbiosis and metabolic inflammation with cardiac arrhythmogenesis. Biomedicines, 9(7), 728. https://doi.org/10.3390/biomedicines9070728 DOI: https://doi.org/10.3390/biomedicines9070728

Crowe, W., Pan, X., Mackle, J., Harris, A., Hardiman, G., Elliott, C. T., & Green, B. D. (2022). Dietary inclusion of nitrite-containing frankfurter exacerbates colorectal cancer pathology and alters metabolism in APCmin mice. Npj Science of Food, 6(1), 60. https://doi.org/10.1038/s41538-022-00174-y DOI: https://doi.org/10.1038/s41538-022-00174-y

Davis, L., Higgs, M., Snaith, A., Lodge, T. A., Strong, J., Espejo-Oltra, J. A., Kujawski, S., Zalewski, P., Pretorius, E., Hoerger, M., & Morten, K. J. (2025). Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia. Frontiers in Neuroscience, 19, 1498981. https://doi.org/10.3389/fnins.2025.1498981 DOI: https://doi.org/10.3389/fnins.2025.1498981

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001). Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). The Journal of the American Medical Association, 285(19), 2486–2497. https://doi.org/10.1001/jama.285.19.2486 DOI: https://doi.org/10.1001/jama.285.19.2486

Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., & Bray, F. (2024). 900-world-fact-sheet.pdf Global Cancer Observatory : Cancer Today. https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf

Fritz, C. D. L., Otegbeye, E. E., Zong, X., Demb, J., Nickel, K. B., Olsen, M. A., Mutch, M., Davidson, N. O., Gupta, S., & Cao, Y. (2023). Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. Journal of the National Cancer Institute, 115(8), 909–916. https://doi.org/10.1093/jnci/djad068 DOI: https://doi.org/10.1093/jnci/djad068

Giuffrè, M., Moretti, R., Campisciano, G., da Silveira, A. B. M., Monda, V. M., Comar, M., Di Bella, S., Antonello, R. M., Luzzati, R., & Crocè, L. S. (2020). You talking to me? Says the Enteric nervous system (ENS) to the microbe. How intestinal microbes interact with the ENS. Journal of Clinical Medicine, 9(11), E3705. https://doi.org/10.3390/jcm9113705 DOI: https://doi.org/10.3390/jcm9113705

Guertin, K. A., Li, X. S., Graubard, B. I., Albanes, D., Weinstein, S. J., Goedert, J. J., Wang, Z., Hazen, S. L., & Sinha, R. (2017). Serum trimethylamine N-oxide, carnitine, choline, and betaine in relation to colorectal cancer risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention study. Cancer Epidemiology, Biomarkers & Prevention, 26(6), 945–952. https://doi.org/10.1158/1055-9965.EPI-16-0948 DOI: https://doi.org/10.1158/1055-9965.EPI-16-0948

Haas, M., Brandl, B., Neuhaus, K., Wudy, S., Kleigrewe, K., Hauner, H., & Skurk, T. (2025). Effect of dietary fiber on trimethylamine-N-oxide production after beef consumption and on gut microbiota: MEATMARK - a randomized cross-over study. European Journal of Clinical Nutrition, 79(10), 980–990. https://doi.org/10.1038/s41430-025-01636-8 DOI: https://doi.org/10.1038/s41430-025-01636-8

He, Q., Fu, Y., Tian, D., & Yan, W. (2018). The contrasting roles of inflammasomes in cancer. American Journal of Cancer Research, 8(4), 566–583.

Helsley, R. N., Miyata, T., Kadam, A., Varadharajan, V., Sangwan, N., Huang, E. C., Banerjee, R., Brown, A. L., Fung, K. K., Massey, W. J., Neumann, C., Orabi, D., Osborn, L. J., Schugar, R. C., McMullen, M. R., Bellar, A., Poulsen, K. L., Kim, A., Pathak, V., … Brown, J. M. (2022). Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice. eLife, 11(e76554), e76554. https://doi.org/10.7554/eLife.76554 DOI: https://doi.org/10.7554/eLife.76554

Hu, C., Zhang, Y., Bi, X., Yao, L., Zhou, Y., & Ding, W. (2022). Correlation between serum trimethylamine-N-oxide concentration and protein energy wasting in patients on maintenance hemodialysis. Renal Failure, 44(1), 1669‑1676. https://doi.org/10.1080/0886022X.2022.2131572 DOI: https://doi.org/10.1080/0886022X.2022.2131572

Huang, J., Chen, X., & Zhong, Q. (2024). Differences in gut microbiota and serum Trimethylamine N-oxide (TMAO) levels in patients with colorectal cancer with a small, nested case-control study. Asian Journal of Agriculture and Biology. 3(12). 2023279. https://doi.org/10.35495/ajab.2023.279 DOI: https://doi.org/10.35495/ajab.2023.279

INDDEX Project. (2018). Data4Diets: Building blocks for diet-related food security analysis. Tufts University. https://inddex.nutrition.tufts.edu/data4diets

Janeiro, M. H., Ramírez, M. J., Milagro, F. I., Martínez, J. A., & Solas, M. (2018). Implication of trimethylamine N-oxide (TMAO) in disease: Potential biomarker or new therapeutic target. Nutrients, 10(10), E1398. https://doi.org/10.3390/nu10101398 DOI: https://doi.org/10.3390/nu10101398

Jarmukhanov, Z., Mukhanbetzhanov, N., Kozhakhmetov, S., Nurgaziyev, M., Sailybayeva, A., Bekbossynova, M., & Kushugulova, A. (2024b). The association between the gut microbiota metabolite trimethylamine N-oxide and heart failure. Frontiers in Microbiology, 15, 1440241. https://doi.org/10.3389/fmicb.2024.1440241 DOI: https://doi.org/10.3389/fmicb.2024.1440241

Jaworska, K., Huc, T., Samborowska, E., Dobrowolski, L., Bielinska, K., Gawlak, M., & Ufnal, M. (2017). Hypertension in rats is associated with an increased permeability of the colon to TMA, a gut bacteria metabolite. PloS One, 12(12), e0189310. https://doi.org/10.1371/journal.pone.0189310 DOI: https://doi.org/10.1371/journal.pone.0189310

Ji, Y., Yin, Y., Sun, L., & Zhang, W. (2020). The molecular and mechanistic insights based on gut-liver axis: Nutritional target for non-alcoholic fatty liver disease (NAFLD) improvement. International Journal of Molecular Sciences, 21(9), E3066. https://doi.org/10.3390/ijms21093066 DOI: https://doi.org/10.3390/ijms21093066

Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015). Colonic bacterial composition in Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 30(10), 1351‑1360. https://doi.org/10.1002/mds.26307 DOI: https://doi.org/10.1002/mds.26307

Knudsen, A. B., Rutter, C. M., Peterse, E. F. P., Lietz, A. P., Seguin, C. L., Meester, R. G. S., Perdue, L. A., Lin, J. S., Siegel, R. L., Doria-Rose, V. P., Feuer, E. J., Zauber, A. G., Kuntz, K. M., & Lansdorp-Vogelaar, I. (2021). Colorectal Cancer Screening : An Updated Modeling Study for the US Preventive Services Task Force. JAMA, 325(19), 1998‑2011. https://doi.org/10.1001/jama.2021.5746 DOI: https://doi.org/10.1001/jama.2021.5746

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., Smith, J. D., DiDonato, J. A., Chen, J., Li, H., Wu, G. D., Lewis, J. D., Warrier, M., Brown, J. M., Krauss, R. M., … Hazen, S. L. (2013). Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine, 19(5), 576‑585. https://doi.org/10.1038/nm.3145 DOI: https://doi.org/10.1038/nm.3145

Li, X., Wang, Y., Xu, J., Luo, K., & Dong, T. (2024). Association between trimethylamine N-oxide and prognosis of patients with myocardial infarction: a meta-analysis. Frontiers in Cardiovascular Medicine, 11, 1334730. https://doi.org/10.3389/fcvm.2024.1334730 DOI: https://doi.org/10.3389/fcvm.2024.1334730

Liñán-Rico, A., Turco, F., Ochoa-Cortes, F., Harzman, A., Needleman, B. J., Arsenescu, R., Abdel-Rasoul, M., Fadda, P., Grants, I., Whitaker, E., Cuomo, R., & Christofi, F. L. (2016). Molecular signaling and dysfunction of the human reactive Enteric glial cell phenotype: Implications for GI infection, IBD, POI, neurological, motility, and GI disorders: Implications for GI infection, IBD, POI, neurological, motility, and GI disorders. Inflammatory Bowel Diseases, 22(8), 1812–1834. https://doi.org/10.1097/MIB.0000000000000854 DOI: https://doi.org/10.1097/MIB.0000000000000854

Lombardo, M., Aulisa, G., Marcon, D., & Rizzo, G. (2022). The influence of animal- or plant-based diets on blood and urine trimethylamine-N-oxide (TMAO) levels in humans. Current Nutrition Reports, 11(1), 56–68. https://doi.org/10.1007/s13668-021-00387-9 DOI: https://doi.org/10.1007/s13668-021-00387-9

Longo, N., Frigeni, M., & Pasquali, M. (2016). Carnitine transport and fatty acid oxidation. Biochimica et Biophysica Acta, 1863(10), 2422–2435. https://doi.org/10.1016/j.bbamcr.2016.01.023 DOI: https://doi.org/10.1016/j.bbamcr.2016.01.023

Loomans-Kropp, H. A., & Umar, A. (2019). Increasing incidence of colorectal cancer in young adults. Journal of Cancer Epidemiology, 2019, 9841295. https://doi.org/10.1155/2019/9841295 DOI: https://doi.org/10.1155/2019/9841295

Ma, G., Pan, B., Chen, Y., Guo, C., Zhao, M., Zheng, L., & Chen, B. (2017). Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion. Bioscience Reports, 37(2), BSR20160244. https://doi.org/10.1042/BSR20160244 DOI: https://doi.org/10.1042/BSR20160244

Maaroufi, Y. (2023). Les Indicateurs sociaux du Maroc. Site institutionnel du Haut-Commissariat au Plan du Royaume du Maroc. Retrieved from: https://www.hcp.ma/Les-Indicateurs-sociaux-du-Maroc-Edition-2023_a3729.html

Mawer, S., & Alhawaj, A. F. (2025). Physiology, Defecation. In StatPearls. StatPearls Publishing. Measurement Toolkit-Food frequency questionnaires. Retrieved from: https://www.measurement-toolkit.org/diet/subjective-methods/food-frequency-questionnaire

Milks, M. W., Velez, M. R., Mehta, N., Ishola, A., Van Houten, T., Yildiz, V. O., Reinbolt, R., Lustberg, M., Smith, S. A., & Orsinelli, D. A. (2018). Usefulness of integrating heart failure risk factors into impairment of global longitudinal strain to predict anthracycline-related cardiac dysfunction. The American Journal of Cardiology, 121(7), 867–873. https://doi.org/10.1016/j.amjcard.2017.12.022 DOI: https://doi.org/10.1016/j.amjcard.2017.12.022

Mueller, K., Karimuddin, A. A., Metcalf, C., Woo, A., & Lefresne, S. (2020). Management of malignant rectal pain and tenesmus: A systematic review. Journal of Palliative Medicine, 23(7), 964–971. https://doi.org/10.1089/jpm.2019.0139 DOI: https://doi.org/10.1089/jpm.2019.0139

Murphy, M. H., Donnelly, P., Breslin, G., Shibli, S., & Nevill, A. M. (2013). Does doing housework keep you healthy? The contribution of domestic physical activity to meeting current recommendations for health. BMC Public Health, 13(1), 966. https://doi.org/10.1186/1471-2458-13-966 DOI: https://doi.org/10.1186/1471-2458-13-966

Naghipour, S., Cox, A. J., Fisher, J. J., Plan, M., Stark, T., West, N., Peart, J. N., Headrick, J. P., & Du Toit, E. F. (2024). Circulating TMAO, the gut microbiome and cardiometabolic disease risk: an exploration in key precursor disorders. Diabetology & Metabolic Syndrome, 16(1), 133. https://doi.org/10.1186/s13098-024-01368-y DOI: https://doi.org/10.1186/s13098-024-01368-y

Oh, J., Kim, J., Lee, S., Park, G., Baritugo, K.-A. G., Han, K. J., Lee, S., & Sung, G.-H. (2024). 1H NMR serum metabolomic change of trimethylamine N-oxide (TMAO) is associated with alcoholic liver disease progression. Metabolites, 14(1), 39. https://doi.org/10.3390/metabo14010039 DOI: https://doi.org/10.3390/metabo14010039

Pandey, S., Skidmore, J., & Dhillon, J. (2025). A systematic review of the effects of diet on the gut Microbiota in individuals at risk for colorectal cancer. In medRxiv. https://doi.org/10.1101/2025.04.14.25325698 DOI: https://doi.org/10.1101/2025.04.14.25325698

Papandreou, C., Moré, M., & Bellamine, A. (2020). Trimethylamine N-oxide in relation to cardiometabolic health-cause or effect? Nutrients, 12(5), E1330. https://doi.org/10.3390/nu12051330 DOI: https://doi.org/10.3390/nu12051330

Rath, S., Heidrich, B., Pieper, D. H., & Vital, M. (2017). Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome, 5(1), 54. https://doi.org/10.1186/s40168-017-0271-9 DOI: https://doi.org/10.1186/s40168-017-0271-9

Registre des Cancers de la Région du Grand Casablanca. (2024). Rapport d’incidence 2018 – 2021 (5ème éd.). Fondation Lalla Salma Prévention et traitement des Cancers. https://www.contrelecancer.ma/site_media/uploaded_files/Registre_des_Cancers_de_la_Region_du_Grand_Casablanca_2018-2021_1_nJ8oeD2.pdf

Sahraoui, S., Acharki, A., Tawfiq, N., Jouhadi, H., Bouras, N., Benider, A., & Kahlain, A. (2000). Colorectal cancer in patients younger than 40 years of age. Cancer radiotherapie: journal de la Societe francaise de radiotherapie oncologique, 4(6), 428–432. https://doi.org/10.1016/s1278-3218(00)00021-4 DOI: https://doi.org/10.1016/S1278-3218(00)00021-4

Stenke, E., Bourke, B., & Knaus, U. (2017). Crohn’s strictures-moving away from the knife. Frontiers in Pediatrics, 5, 141. https://doi.org/10.3389/fped.2017.00141 DOI: https://doi.org/10.3389/fped.2017.00141

Sun, Y., Lin, X., Liu, Z., Hu, L., Sun, P., Shen, G., Fan, F., Zhang, Y., & Li, J. (2024). Association between plasma trimethylamine N-oxide and coronary heart disease: new insights on sex and age differences. Frontiers in Cardiovascular Medicine, 11, 1397023. https://doi.org/10.3389/fcvm.2024.1397023 DOI: https://doi.org/10.3389/fcvm.2024.1397023

Sung, H., Siegel, R. L., Laversanne, M., Jiang, C., Morgan, E., Zahwe, M., Cao, Y., Bray, F., & Jemal, A. (2025). Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data. The Lancet Oncology, 26(1), 51–63. https://doi.org/10.1016/S1470-2045(24)00600-4 DOI: https://doi.org/10.1016/S1470-2045(24)00600-4

Turco, F., Sarnelli, G., Cirillo, C., Palumbo, I., De Giorgi, F., D’Alessandro, A., Cammarota, M., Giuliano, M., & Cuomo, R. (2014). Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signaling in human enteric glial cells. Gut, 63(1), 105–115. https://doi.org/10.1136/gutjnl-2012-302090 DOI: https://doi.org/10.1136/gutjnl-2012-302090

Vecchio, M., Chiaramonte, R., Testa, G., & Pavone, V. (2021). Clinical effects of L-carnitine supplementation on physical performance in healthy subjects, the key to success in rehabilitation: A systematic review and meta-analysis from the rehabilitation Point of View. Journal of Functional Morphology and Kinesiology, 6(4), 93. https://doi.org/10.3390/jfmk6040093 DOI: https://doi.org/10.3390/jfmk6040093

Wang, H., Luo, Q., Feng, X., Zhang, R., Li, J., & Chen, F. (2018). NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma. BMC Cancer, 18(1), 500. https://doi.org/10.1186/s12885-018-4403-9 DOI: https://doi.org/10.1186/s12885-018-4403-9

Wang, Hai, Rong, X., Zhao, G., Zhou, Y., Xiao, Y., Ma, D., Jin, X., Wu, Y., Yan, Y., Yang, H., Zhou, Y., Qian, M., Niu, C., Hu, X., Li, D.-Q., Liu, Q., Wen, Y., Jiang, Y.-Z., Zhao, C., & Shao, Z.-M. (2022a). The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer. Cell Metabolism, 34(4), 581-594.e8. https://doi.org/10.1016/j.cmet.2022.02.010 DOI: https://doi.org/10.1016/j.cmet.2022.02.010

Wang, L., Nan, Y., Zhu, W., & Wang, S. (2023a). Effect of TMAO on the incidence and prognosis of cerebral infarction: a systematic review and meta-analysis. Frontiers in Neurology, 14, 1287928. https://doi.org/10.3389/fneur.2023.1287928 DOI: https://doi.org/10.3389/fneur.2023.1287928

Wang, M., Wang, Z., Lee, Y., Lai, H. T. M., de Oliveira Otto, M. C., Lemaitre, R. N., Fretts, A., Sotoodehnia, N., Budoff, M., DiDonato, J. A., McKnight, B., Tang, W. H. W., Psaty, B. M., Siscovick, D. S., Hazen, S. L., & Mozaffarian, D. (2022b). Dietary meat, trimethylamine N-oxide-related metabolites, and incident cardiovascular disease among older adults: The cardiovascular health study. Arteriosclerosis, Thrombosis, and Vascular Biology, 42(9), e273–e288. https://doi.org/10.1161/ATVBAHA.121.316533 DOI: https://doi.org/10.1161/ATVBAHA.121.316533

Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021). The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options. Brain: A Journal of Neurology, 144(9), 2571–2593. https://doi.org/10.1093/brain/awab156 DOI: https://doi.org/10.1093/brain/awab156

Wang, Q., Yang, Q., & Liu, X. (2023b). The microbiota-gut-brain axis and neurodevelopmental disorders. Protein & Cell, 14(10), 762–775. https://doi.org/10.1093/procel/pwad026 DOI: https://doi.org/10.1093/procel/pwad026

Wang, S., Luo, H., Zou, Z.-H., Su, M.-L., Pan, Z.-H., Wang, M., & Zhang, W.-J. (2025). Trimethylamine N-oxide and smoking are associated with the progression of thromboangiitis obliterans. The Journal of Surgical Research, 311, 78–85. https://doi.org/10.1016/j.jss.2025.04.018 DOI: https://doi.org/10.1016/j.jss.2025.04.018

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., Krauss, R. M., & Hazen, S. L. (2019). 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. European Heart Journal, 40(7), 583–594. https://doi.org/10.1093/eurheartj/ehy799 DOI: https://doi.org/10.1093/eurheartj/ehy799

Wilcox, J., Skye, S. M., Graham, B., Zabell, A., Li, X. S., Li, L., Shelkay, S., Fu, X., Neale, S., O’Laughlin, C., Peterson, K., Hazen, S. L., & Tang, W. H. W. (2021). Dietary choline supplements, but not eggs, raise fasting TMAO levels in participants with normal renal function: A randomized clinical trial. The American Journal of Medicine, 134(9), 1160-1169.e3. https://doi.org/10.1016/j.amjmed.2021.03.016 DOI: https://doi.org/10.1016/j.amjmed.2021.03.016

Xie, S., Deng, N., Fang, L., Shen, J., Tan, Z., & Cai, Y. (2024a). TMAO is involved in kidney-yang deficiency syndrome diarrhea by mediating the “gut-kidney axis.” Heliyon, 10(15), e35461. https://doi.org/10.1016/j.heliyon.2024.e35461 DOI: https://doi.org/10.1016/j.heliyon.2024.e35461

Xie, S., Fang, L., Deng, N., Shen, J., Tan, Z., & Peng, X. (2024b). Targeting the gut-kidney axis in diarrhea with kidney-yang deficiency syndrome: The role of Sishen Pills in regulating TMAO-mediated inflammatory response. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 30, e944185. https://doi.org/10.12659/MSM.944185 DOI: https://doi.org/10.12659/MSM.944185

Xu, R., Wang, Q., & Li, L. (2015). A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics, 16 Suppl 7(S7), S4. https://doi.org/10.1186/1471-2164-16-S7-S4 DOI: https://doi.org/10.1186/1471-2164-16-S7-S4

Yang, S., Dai, H., Lu, Y., Li, R., Gao, C., & Pan, S. (2022). Trimethylamine N-oxide promotes cell proliferation and angiogenesis in colorectal cancer. Journal of Immunology Research, 2022, 7043856. https://doi.org/10.1155/2022/7043856 DOI: https://doi.org/10.1155/2022/7043856

Yao, N., Li, W., Xu, G., Duan, N., Yu, G., & Qu, J. (2023). Choline metabolism and its implications in cancer. Frontiers in Oncology, 13, 1234887. https://doi.org/10.3389/fonc.2023.1234887 DOI: https://doi.org/10.3389/fonc.2023.1234887

Yin, X., Gibbons, H., Rundle, M., Frost, G., McNulty, B. A., Nugent, A. P., Walton, J., Flynn, A., & Brennan, L. (2020). The relationship between fish intake and urinary trimethylamine-N-oxide. Molecular Nutrition & Food Research, 64(3), e1900799. https://doi.org/10.1002/mnfr.201900799 DOI: https://doi.org/10.1002/mnfr.201900799

Yuan, X., Wei, X., Liu, J., Tang, C., Peng, L., Wang, H., & Huang, Y. (2023). Association of circulating trimethylamine-N oxide with malnutrition and the risk of coronary artery disease in patients with maintenance hemodialysis. Journal of Renal Nutrition: The Official Journal of the Council on Renal Nutrition of the National Kidney Foundation, 33(3), 465–471. https://doi.org/10.1053/j.jrn.2022.11.001 DOI: https://doi.org/10.1053/j.jrn.2022.11.001

Yue, C., Yang, X., Li, J., Chen, X., Zhao, X., Chen, Y., & Wen, Y. (2017). Trimethylamine N-oxide prime NLRP3 inflammasome via inhibiting ATG16L1-induced autophagy in colonic epithelial cells. Biochemical and Biophysical Research Communications, 490(2), 541–551. https://doi.org/10.1016/j.bbrc.2017.06.075 DOI: https://doi.org/10.1016/j.bbrc.2017.06.075

Zhen, J., Zhou, Z., He, M., Han, H.-X., Lv, E.-H., Wen, P.-B., Liu, X., Wang, Y.-T., Cai, X.-C., Tian, J.-Q., Zhang, M.-Y., Xiao, L., & Kang, X.-X. (2023). The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Frontiers in Endocrinology, 14, 1085041. https://doi.org/10.3389/fendo.2023.1085041 DOI: https://doi.org/10.3389/fendo.2023.1085041

Zheng, X., Hur, J., Nguyen, L. H., Liu, J., Song, M., Wu, K., Smith-Warner, S. A., Ogino, S., Willett, W. C., Chan, A. T., Giovannucci, E., & Cao, Y. (2021). Comprehensive assessment of diet quality and risk of precursors of early-onset colorectal cancer. Journal of the National Cancer Institute, 113(5), 543–552. https://doi.org/10.1093/jnci/djaa164 DOI: https://doi.org/10.1093/jnci/djaa164