{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:28:09Z","timestamp":1790677689303,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007917","name":"USDA, Agricultural Research Service","doi-asserted-by":"publisher","award":["2032-51530-025-00D"],"award-info":[{"award-number":["2032-51530-025-00D"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007917","name":"USDA, Agricultural Research Service","doi-asserted-by":"publisher","award":["2032-51530-026-00-D"],"award-info":[{"award-number":["2032-51530-026-00-D"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007917","name":"USDA, Agricultural Research Service","doi-asserted-by":"publisher","award":["R01HL148110"],"award-info":[{"award-number":["R01HL148110"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007917","name":"USDA, Agricultural Research Service","doi-asserted-by":"publisher","award":["R01133169"],"award-info":[{"award-number":["R01133169"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["2032-51530-025-00D"],"award-info":[{"award-number":["2032-51530-025-00D"]}]},{"name":"National Institute of Health","award":["2032-51530-026-00-D"],"award-info":[{"award-number":["2032-51530-026-00-D"]}]},{"name":"National Institute of Health","award":["R01HL148110"],"award-info":[{"award-number":["R01HL148110"]}]},{"name":"National Institute of Health","award":["R01133169"],"award-info":[{"award-number":["R01133169"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plasma trimethylamine n-oxide (TMAO) concentration increases in responses to feeding TMAO, choline, phosphatidylcholine, L-carnitine, and betaine but it is unknown whether concentrations change following a mixed macronutrient tolerance test (MMTT) with limited amounts of TMAO precursors. In this proof-of-concept study, we provided healthy female and male adults (n = 97) ranging in age (18\u201365 years) and BMI (18\u201344 kg\/m2) a MMTT (60% fat, 25% sucrose; 42% of a standard 2000 kilo calorie diet) and recorded their metabolic response at fasting and at 30 min, 3 h, and 6 h postprandially. We quantified total exposure to TMAO (AUC-TMAO) and classified individuals by the blood draw at which they experienced their maximal TMAO concentration (TMAO-response groups). We related AUC-TMAO to the 16S rRNA microbiome, to two SNPs in the exons of the FMO3 gene (rs2266782, G&gt;A, p.Glu158Lys; and rs2266780, A&gt;G, p.Glu308Gly), and to a priori plasma metabolites. We observed varying TMAO responses (timing and magnitude) and identified a sex by age interaction such that AUC-TMAO increased with age in females but not in males (p-value = 0.0112). Few relationships between AUC-TMAO and the fecal microbiome and FMO3 genotype were identified. We observed a strong correlation between AUC-TMAO and TNF-\u03b1 that depended on TMAO-response group. These findings promote precision nutrition and have important ramifications for the eating behavior of adults who could benefit from reducing TMAO exposure, and for understanding factors that generate plasma TMAO.<\/jats:p>","DOI":"10.3390\/ijms24032074","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:52:41Z","timestamp":1674197561000},"page":"2074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3704-3560","authenticated-orcid":false,"given":"Kristen L.","family":"James","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik R.","family":"Gertz","sequence":"additional","affiliation":[{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine P.","family":"Kirschke","sequence":"additional","affiliation":[{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooman","family":"Allayee","sequence":"additional","affiliation":[{"name":"Department of Population & Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Department of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-6539","authenticated-orcid":false,"given":"Mary E.","family":"Kable","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-6571","authenticated-orcid":false,"given":"John W.","family":"Newman","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Stephensen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Psychogios, N., Hau, D.D., Peng, J., Guo, A.C., Mandal, R., Bouatra, S., Sinelnikov, I., Krishnamurthy, R., Eisner, R., and Gautam, B. 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