Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men

Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO re...

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Published inNutrients Vol. 12; no. 8; p. 2220
Main Authors Cho, Clara E., Aardema, Niklas D. J., Bunnell, Madison L., Larson, Deanna P., Aguilar, Sheryl S., Bergeson, Janet R., Malysheva, Olga V., Caudill, Marie A., Lefevre, Michael
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 25.07.2020
MDPI
Subjects
Adult
Biomarkers - blood
Biomarkers - urine
Blood
cardiovascular diseases
Cardiovascular Diseases - etiology
choline
Choline - administration & dosage
Clostridium
Cross-Over Studies
Diet - adverse effects
Dietary Supplements
digestive system
Double-Blind Method
Female
Gastrointestinal Microbiome - drug effects
Gut microbiota
Healthy Volunteers
Heart Disease Risk Factors
Humans
intestinal microorganisms
Lachnospiraceae
Male
Meals
Meals - physiology
metabolites
Methylamines - blood
Methylamines - urine
microbiome
Microbiota
Middle Aged
multivariate analysis
Nutrition
phosphatidylcholines
Phosphatidylcholines - administration & dosage
risk factors
Ruminococcaceae
Urine
Womens health
United States > US
Utah
trimethylamine-N-oxide
choline
metabolism
dietary precursor intake
gut microbiota
Online AccessGet full text

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Abstract Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk
AbstractList Background: Trimethylamine- N -oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men ( n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC ( p = 0.01) and 2.5-times greater urinary TMAO change from baseline ( p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk
Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk
Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response.BACKGROUNDTrimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response.In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control.METHODSIn a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control.Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05).RESULTSCholine bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05).Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.CONCLUSIONGiven that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.
Trimethylamine- -oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. In a randomized, controlled, double-blinded, crossover study, healthy men ( = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Choline bitartrate yielded three-times greater plasma TMAO AUC ( = 0.01) and 2.5-times greater urinary TMAO change from baseline ( = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of from and compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; < 0.05). Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.
Author Aardema, Niklas D. J.
Bergeson, Janet R.
Caudill, Marie A.
Aguilar, Sheryl S.
Cho, Clara E.
Malysheva, Olga V.
Larson, Deanna P.
Lefevre, Michael
Bunnell, Madison L.
AuthorAffiliation 2 Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; ovm4@cornell.edu (O.V.M.); mac379@cornell.edu (M.A.C.)
1 Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, UT 84322, USA; niklas.aardema@usu.edu (N.D.J.A.); maddielbunnell@gmail.com (M.L.B.); dpassarolarson@gmail.com (D.P.L.); sheryl.aguilar@usu.edu (S.S.A.); janet.bergeson@usu.edu (J.R.B.); michael.lefevre@usu.edu (M.L.)
AuthorAffiliation_xml – name: 2 Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; ovm4@cornell.edu (O.V.M.); mac379@cornell.edu (M.A.C.)
– name: 1 Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, UT 84322, USA; niklas.aardema@usu.edu (N.D.J.A.); maddielbunnell@gmail.com (M.L.B.); dpassarolarson@gmail.com (D.P.L.); sheryl.aguilar@usu.edu (S.S.A.); janet.bergeson@usu.edu (J.R.B.); michael.lefevre@usu.edu (M.L.)
Author_xml – sequence: 1
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  surname: Cho
  fullname: Cho, Clara E.
– sequence: 2
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  surname: Bunnell
  fullname: Bunnell, Madison L.
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  surname: Larson
  fullname: Larson, Deanna P.
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  surname: Aguilar
  fullname: Aguilar, Sheryl S.
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  fullname: Bergeson, Janet R.
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  surname: Malysheva
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  surname: Lefevre
  fullname: Lefevre, Michael
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32722424$$D View this record in MEDLINE/PubMed
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Cites_doi 10.3945/ajcn.114.087692
10.1093/molbev/mst010
10.1093/jn/133.5.1302
10.1096/fj.201700692RR
10.1056/NEJMoa1109400
10.3390/nu10121971
10.3945/ajcn.111.022772
10.1016/j.celrep.2017.06.053
10.1080/07315724.2017.1365026
10.1038/nature09922
10.1146/annurev.nu.01.070181.000523
10.1080/07315724.2018.1466213
10.1038/nm.3145
10.1186/2047-217X-2-16
10.1073/pnas.1215689109
10.3390/nu11102548
10.1073/pnas.0504978102
10.1016/j.gene.2013.03.010
10.1111/j.1471-4159.1977.tb07732.x
10.1002/jms.1339
10.1111/j.1753-4887.2009.00246.x
10.1002/mnfr.201770016
10.7326/0003-4819-150-9-200905050-00006
10.1016/j.yclnex.2016.10.002
10.1016/j.bcp.2013.03.020
10.2174/1389200054021807
10.1096/fj.12-221648
10.1038/nmeth.3869
10.1373/49.2.286
10.3945/ajcn.110.005975
10.1021/ac025624x
10.1146/annurev.nutr.26.061505.111156
10.1128/AEM.03006-05
10.1128/AEM.01043-13
10.1128/mBio.02481-14
10.1096/fj.12-207894
10.1016/j.jnutbio.2017.02.010
10.1128/AEM.71.12.8228-8235.2005
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choline
metabolism
dietary precursor intake
gut microbiota
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References Ley (ref_10) 2005; 102
Yan (ref_8) 2012; 95
Levey (ref_13) 2009; 150
Craciun (ref_35) 2012; 109
ref_36
Johnson (ref_15) 2008; 43
ref_33
Yamazaki (ref_26) 2013; 85
ref_31
Zeisel (ref_32) 1981; 1
Taesuwan (ref_12) 2017; 45
DeSantis (ref_22) 2006; 72
Koeth (ref_39) 2013; 19
Koc (ref_16) 2002; 74
Holm (ref_17) 2003; 49
ref_19
Katoh (ref_23) 2013; 30
ref_37
Growdon (ref_6) 1977; 28
Yan (ref_18) 2011; 93
Callahan (ref_21) 2016; 13
Bain (ref_11) 2005; 6
Schugar (ref_38) 2017; 20
Wang (ref_2) 2011; 472
Missimer (ref_34) 2018; 37
Jiang (ref_43) 2013; 27
Tang (ref_1) 2013; 368
Zeisel (ref_5) 1983; 225
Cashman (ref_30) 2001; 29
Miller (ref_7) 2014; 100
Zeisel (ref_3) 2003; 133
Demirkaya (ref_27) 2013; 521
Cho (ref_14) 2016; 10
Kozich (ref_20) 2013; 79
Caudill (ref_44) 2018; 32
Zeisel (ref_41) 2006; 26
Lozupone (ref_25) 2005; 71
ref_28
Zeisel (ref_40) 2009; 67
ref_9
Jiang (ref_42) 2012; 26
Pirrung (ref_24) 2013; 2
ref_4
Mandal (ref_29) 2015; 26
References_xml – volume: 100
  start-page: 778
  year: 2014
  ident: ref_7
  article-title: Effect of egg ingestion on trimethylamine-N-oxide production in humans: A randomized, controlled, dose-response study
  publication-title: Am. J. Clin. Nutr.
  doi: 10.3945/ajcn.114.087692
– ident: ref_28
– volume: 30
  start-page: 772
  year: 2013
  ident: ref_23
  article-title: MAFFT multiple sequence alignment software version 7: Improvements in performance and usability
  publication-title: Mol. Biol. Evol.
  doi: 10.1093/molbev/mst010
– volume: 133
  start-page: 1302
  year: 2003
  ident: ref_3
  article-title: Concentrations of choline-containing compounds and betaine in common foods
  publication-title: J. Nutr.
  doi: 10.1093/jn/133.5.1302
– volume: 32
  start-page: 2172
  year: 2018
  ident: ref_44
  article-title: Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: A randomized, double-blind, controlled feeding study
  publication-title: FASEB J.
  doi: 10.1096/fj.201700692RR
– volume: 368
  start-page: 1575
  year: 2013
  ident: ref_1
  article-title: Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1109400
– ident: ref_37
  doi: 10.3390/nu10121971
– volume: 95
  start-page: 1060
  year: 2012
  ident: ref_8
  article-title: Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans
  publication-title: Am. J. Clin. Nutr.
  doi: 10.3945/ajcn.111.022772
– volume: 20
  start-page: 279
  year: 2017
  ident: ref_38
  article-title: The TMAO-producing enzyme flavin-containing monooxygenase 3 regulates obesity and the beiging of white adipose tissue
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2017.06.053
– volume: 37
  start-page: 140
  year: 2018
  ident: ref_34
  article-title: Compared to an oatmeal breakfast, two eggs/day increased plasma carotenoids and choline without increasing trimethyl amine n-oxide concentrations
  publication-title: J. Am. Coll. Nutr.
  doi: 10.1080/07315724.2017.1365026
– volume: 472
  start-page: 57
  year: 2011
  ident: ref_2
  article-title: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
  publication-title: Nature
  doi: 10.1038/nature09922
– volume: 1
  start-page: 95
  year: 1981
  ident: ref_32
  article-title: Dietary choline: Biochemistry, physiology, and pharmacology
  publication-title: Annu. Rev. Nutr.
  doi: 10.1146/annurev.nu.01.070181.000523
– ident: ref_33
  doi: 10.1080/07315724.2018.1466213
– volume: 19
  start-page: 576
  year: 2013
  ident: ref_39
  article-title: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
  publication-title: Nat. Med.
  doi: 10.1038/nm.3145
– volume: 2
  start-page: 16
  year: 2013
  ident: ref_24
  article-title: EMPeror: A tool for visualizing high-throughput microbial community data
  publication-title: Gigascience
  doi: 10.1186/2047-217X-2-16
– volume: 109
  start-page: 21307
  year: 2012
  ident: ref_35
  article-title: Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1215689109
– ident: ref_31
  doi: 10.3390/nu11102548
– volume: 102
  start-page: 11070
  year: 2005
  ident: ref_10
  article-title: Obesity alters gut microbial ecology
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0504978102
– volume: 521
  start-page: 116
  year: 2013
  ident: ref_27
  article-title: Flavin containing monooxygenase 3 genetic polymorphisms Glu158Lys and Glu308Gly and their relation to ischemic stroke
  publication-title: Gene
  doi: 10.1016/j.gene.2013.03.010
– volume: 28
  start-page: 229
  year: 1977
  ident: ref_6
  article-title: Effects of oral choline administration on serum and CSF choline levels in patients with Huntington’s disease
  publication-title: J. Neurochem.
  doi: 10.1111/j.1471-4159.1977.tb07732.x
– volume: 43
  start-page: 495
  year: 2008
  ident: ref_15
  article-title: A flow injection electrospray ionization tandem mass spectrometric method for the simultaneous measurement of trimethylamine and trimethylamine N-oxide in urine
  publication-title: J. Mass Spectrom.
  doi: 10.1002/jms.1339
– volume: 67
  start-page: 615
  year: 2009
  ident: ref_40
  article-title: Choline: An essential nutrient for public health
  publication-title: Nutr. Rev.
  doi: 10.1111/j.1753-4887.2009.00246.x
– ident: ref_9
  doi: 10.1002/mnfr.201770016
– volume: 150
  start-page: 604
  year: 2009
  ident: ref_13
  article-title: A new equation to estimate glomerular filtration rate
  publication-title: Ann. Intern. Med.
  doi: 10.7326/0003-4819-150-9-200905050-00006
– volume: 10
  start-page: 1
  year: 2016
  ident: ref_14
  article-title: Choline and one-carbon metabolite response to egg, beef and fish among healthy young men: A short-term randomized clinical study
  publication-title: Clin. Nutr. Exper.
  doi: 10.1016/j.yclnex.2016.10.002
– volume: 85
  start-page: 1588
  year: 2013
  ident: ref_26
  article-title: Survey of variants of human flavin-containing monooxygenase 3 (FMO3) and their drug oxidation activities
  publication-title: Biochem. Pharmacol.
  doi: 10.1016/j.bcp.2013.03.020
– volume: 6
  start-page: 227
  year: 2005
  ident: ref_11
  article-title: Trimethylamine: Metabolic, pharmacokinetic and safety aspects
  publication-title: Curr. Drug Metab.
  doi: 10.2174/1389200054021807
– volume: 27
  start-page: 1245
  year: 2013
  ident: ref_43
  article-title: A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1)
  publication-title: FASEB J.
  doi: 10.1096/fj.12-221648
– ident: ref_4
– volume: 26
  start-page: 27663
  year: 2015
  ident: ref_29
  article-title: Analysis of composition of microbiomes: A novel method for studying microbial composition
  publication-title: Microb. Ecol. Health Dis.
– volume: 13
  start-page: 581
  year: 2016
  ident: ref_21
  article-title: DADA2: High-resolution sample inference from Illumina amplicon data
  publication-title: Nat. Methods
  doi: 10.1038/nmeth.3869
– volume: 49
  start-page: 286
  year: 2003
  ident: ref_17
  article-title: Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry
  publication-title: Clin. Chem.
  doi: 10.1373/49.2.286
– volume: 93
  start-page: 348
  year: 2011
  ident: ref_18
  article-title: MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline
  publication-title: Am. J. Clin. Nutr.
  doi: 10.3945/ajcn.110.005975
– volume: 74
  start-page: 4734
  year: 2002
  ident: ref_16
  article-title: Quantitation of choline and its metabolites in tissues and foods by liquid chromatography/electrospray ionization-isotope dilution mass spectrometry
  publication-title: Anal. Chem.
  doi: 10.1021/ac025624x
– volume: 26
  start-page: 229
  year: 2006
  ident: ref_41
  article-title: Choline: Critical role during fetal development and dietary requirements in adults
  publication-title: Annu. Rev. Nutr.
  doi: 10.1146/annurev.nutr.26.061505.111156
– volume: 72
  start-page: 5069
  year: 2006
  ident: ref_22
  article-title: Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB
  publication-title: Appl. Environ. Microbiol.
  doi: 10.1128/AEM.03006-05
– volume: 225
  start-page: 320
  year: 1983
  ident: ref_5
  article-title: Formation of methylamines from ingested choline and lecithin
  publication-title: J. Pharmacol. Exp. Ther.
– volume: 79
  start-page: 5112
  year: 2013
  ident: ref_20
  article-title: Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform
  publication-title: Appl. Environ. Microbiol.
  doi: 10.1128/AEM.01043-13
– volume: 29
  start-page: 1629
  year: 2001
  ident: ref_30
  article-title: Population distribution of human flavin-containing monooxygenase form 3: Gene polymorphisms
  publication-title: Drug Metab. Dispos.
– ident: ref_19
– ident: ref_36
  doi: 10.1128/mBio.02481-14
– volume: 26
  start-page: 3563
  year: 2012
  ident: ref_42
  article-title: Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans
  publication-title: FASEB J.
  doi: 10.1096/fj.12-207894
– volume: 45
  start-page: 77
  year: 2017
  ident: ref_12
  article-title: The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans
  publication-title: J. Nutr. Biochem.
  doi: 10.1016/j.jnutbio.2017.02.010
– volume: 71
  start-page: 8228
  year: 2005
  ident: ref_25
  article-title: UniFrac: A new phylogenetic method for comparing microbial communities
  publication-title: Appl. Environ. Microbiol.
  doi: 10.1128/AEM.71.12.8228-8235.2005
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Snippet Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease....
Trimethylamine- -oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought...
Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought...
Background: Trimethylamine- N -oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular...
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StartPage 2220
SubjectTerms Adult
Biomarkers - blood
Biomarkers - urine
Blood
cardiovascular diseases
Cardiovascular Diseases - etiology
choline
Choline - administration & dosage
Clostridium
Cross-Over Studies
Diet - adverse effects
Dietary Supplements
digestive system
Double-Blind Method
Female
Gastrointestinal Microbiome - drug effects
Gut microbiota
Healthy Volunteers
Heart Disease Risk Factors
Humans
intestinal microorganisms
Lachnospiraceae
Male
Meals
Meals - physiology
metabolites
Methylamines - blood
Methylamines - urine
microbiome
Microbiota
Middle Aged
multivariate analysis
Nutrition
phosphatidylcholines
Phosphatidylcholines - administration & dosage
risk factors
Ruminococcaceae
Urine
Womens health
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Title Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men
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Volume 12
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