title: Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk.
abstract: Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51-53 %E) v. lower CHO (39-40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine and γ-butyrobetaine concentrations were higher after the high- v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by high v. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.
authors.affiliation: 1Children's Hospital Oakland Research Institute,Oakland,CA 94609,USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bergeron
authors.affiliation: 3Lawrence Berkeley National Laboratory,Department of Genome Sciences,Life Sciences Division,Berkeley,CA 94720,USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Williams
authors.affiliation: 4Juniata College,Huntingdon,PA 16652,USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Lamendella
authors.affiliation: 1Children's Hospital Oakland Research Institute,Oakland,CA 94609,USA.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Faghihnia
authors.affiliation: 4Juniata College,Huntingdon,PA 16652,USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Grube
authors.affiliation: 5Department of Cellular & Molecular Medicine,Cleveland Clinic,Cleveland,OH 44195,USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: 5Department of Cellular & Molecular Medicine,Cleveland Clinic,Cleveland,OH 44195,USA.
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 6Departments of Pediatrics and Computer Science & Engineering,University of California San Diego,San Diego,CA 92093,USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.affiliation: 8Pacific Northwest National Laboratory,Biological Sciences Division,Richland,WA 99352,USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
authors.affiliation: 5Department of Cellular & Molecular Medicine,Cleveland Clinic,Cleveland,OH 44195,USA.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: 1Children's Hospital Oakland Research Institute,Oakland,CA 94609,USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002140:California / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects; D050528:Diet, Carbohydrate-Restricted; D064806:Dysbiosis / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D006946:Hyperinsulinism / Q000517:prevention & control; D007333:Insulin Resistance; D008297:Male; D008744:Methylamines / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000382:microbiology / Q000503:physiopathology; D050177:Overweight / Q000382:microbiology / Q000503:physiopathology; D012306:Risk; D013213:Starch / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D008744:Methylamines; D013213:Starch; C005855:trimethyloxamine
keywords:  HOMA-IR homoeostatic model assessment of insulin resistance;  RS resistant starches;  TMAO trimethylamine-N-oxide; CVD; Carbohydrate; Glucose; Insulin; Lipids; Resistant starch; Trimethylamine-N-oxide