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Cited by 127Gut microbiota and healthProbiotics and Fermented FoodsNutritional Studies and Diet

Probiotic supplementation and trimethylamine‐N‐oxide production following a high‐fat diet

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Boutagy, Nabil E., Neilson, Andrew P., Osterberg, Kristin L., Smithson, Andrew T., Englund, Tessa R., Davy, Brenda M., Hulver, Matthew W., Davy, Kevin P.·2015·Obesity
DOI 10.1002/oby.21212
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Abstract

OBJECTIVE: The objective of this study was to test the hypothesis that the multi-strain probiotic VSL#3 would attenuate the increase in fasting plasma concentrations of trimethylamine-N-oxide (TMAO) following a high-fat diet. METHODS: Nineteen healthy, non-obese males (18-30 years) participated in the present study. Following a 2-week eucaloric control diet, subjects were randomized to either VSL#3 (900 billion live bacteria) or placebo (cornstarch) during the consumption of a hypercaloric (+1,000 kcal day(-1) ), high-fat diet (55% fat) for 4 weeks. Plasma TMAO, L-carnitine, choline, and betaine (UPLC-MS/MS) were measured at baseline and following a high-fat diet. RESULTS: Plasma TMAO significantly increased 89% ± 66% vs. 115% ± 61% in both the VSL#3 and placebo groups, respectively; however, the magnitude of change in plasma TMAO was not different (P > 0.05) between them. Plasma L-carnitine, choline, and betaine concentrations did not increase following the high-fat diet in either group. CONCLUSIONS: A high-fat diet increases plasma TMAO in healthy, normal-weight, young males. However, VSL#3 treatment does not appear to influence plasma TMAO concentrations following a high-fat diet. Future studies are needed to determine whether other therapeutic strategies can attenuate the production of TMAO.

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References 39 · Cited by 127

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  1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2015 update: a report from the American heart association. Circulation 2015;131(4):e29-322.
  2. Bernstein AM, Sun Q, Hu FB, Stampfer MJ, Manson JE, Willett WC. Major dietary protein sources and risk of coronary heart disease in women. Circulation 2010;122:876-883.
  3. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013;19:576-585.
  4. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-63.
  5. Wang Z, Tang WW, Buffa JA, et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Hear J 2014;35:904-910
  6. Lang D, Yeung C, Peter R, et al. Isoform specificity of trimethylamine-N- oxygenation by human flavin-containing monooxygenase (FMO) and P450 enzymes: selective catalysis by fmo3. Biochem Pharmacol 1998;56:1005-1012.
  7. Martin F-PJ, Wang Y, Sprenger N, et al. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Systems Biol 2008;4:1-21.
  8. Shimizu M, Cashman JR, Yamazaki H. Transient trimethylaminuria related to menstruation. BMC Med Genet 2007;8:1-3.
  9. Spanhaak S, Havenaar R, Schaafsma G. The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans. Eur J Clin Nutr 1998;52:899-907.
  10. Brigidi P, Swennen E, Vitali B, Rossi M, Matteuzzi D. PCR detection of Bifidobacterium strains and Streptococcus thermophilus in feces of human subjects after oral bacteriotherapy and yogurt consumption. Int J Food Microbiol 2003;81: 203-209.
  11. Matsumoto K, Takada T, Shimizu K, et al. Effects of a probiotic fermented milk beverage containing Lactobacillus casei strain Shirota on defecation frequency, intestinal microbiota, and the intestinal environment of healthy individuals with soft stools. J Biosci Bioeng 2010;110:547-552.
  12. Nagata S, Asahara T, Ohta T, et al. Effect of the continuous intake of probiotic- fermented milk containing Lactobacillus casei strain Shirota on fever in a mass outbreak of norovirus gastroenteritis and the faecal microflora in a health service facility for the aged. Br J Nutr 2011;106:549-556.
  13. Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL# 3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 2009;7:1202.
  14. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124:1202-1209.
  15. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000;119:305.
  16. Brigidi P, Vitali B, Swennen E, Bazzocchi G, Matteuzzi D. Effects of probiotic administration upon the composition and enzymatic activity of human fecal microbiota in patients with irritable bowel syndrome or functional diarrhea. Res Microbiol 2001;152:735-741.
  17. Chapman TM, Plosker GL, Figgitt DP. VSL# 3 probiotic mixture. Drugs 2006;66: 1371-1387.
  18. Institute of Medicine of the National Academies. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. National Academies Press; Washington D.C., 2005.
  19. Werner TJ, Boutagy NE, Osterberg KL, Rivero JM, Davy KP. Singular and combined effects of nebivolol and lifestyle modification on large artery stiffness in hypertensive adults. Ther Adv Cardiovasc Dis 2013;7:285-292.
  20. Demarquoy J, Georges B, Rigault C, et al. Radioisotopic determination of L- carnitine content in foods commonly eaten in Western countries. Food Chem 2004; 86:137-142.
  21. Shils ME, Shike M. Modern Nutrition in Health and Disease, 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2006.
  22. Brigidi P, Vitali B, Swennen E, Altomare L, Rossi M, Matteuzzi D. Specific detection of Bifidobacterium strains in a pharmaceutical probiotic product and in human feces by polymerase chain reaction. Syst Appl Microbiol 2000;23:391-399.
  23. Desai AS, Mitchell GF, Fang JC, Creager MA. Central aortic stiffness is increased in patients with heart failure and preserved ejection fraction. J Cardiac Failure 2009;15:658-664.
  24. Kirsch SH, Herrmann W, Rabagny Y, Obeid R. Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable- isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2010;878:3338-3344.
  25. Vinj e S, Stroes E, Nieuwdorp M, Hazen SL. The gut microbiome as novel cardio- metabolic target: the time has come! Eur Heart J 2013;38(14):883-887.
  26. Rebouche CJ. Kinetics, Pharmacokinetics, and Regulation of l-Carnitine and Acetyl-l-Carnitine Metabolism. Ann N Y Acad Sci 2004;1033:30-41.
  27. Sanaie S, Ebrahimi-Mameghani M, Mahmoodpoor A, Shadvar K, Golzari SE. Effect of a probiotic preparation (VSL#3) on cardiovascularrisk parameters in critically-ill patients. J Cardiovasc Thoracic Res 2013;5:67-70.
  28. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Therap 2014;39:1276-1285.
  29. Rehman A, Heinsen FA, Koenen ME, et al. Effects of probiotics and antibiotics on the intestinal homeostasis in a computer controlled model of the large intestine. BMC Microbiol 2012;12:47.
  30. Mencarelli A, Distrutti E, Renga B, et al. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PloS One 2011;6:e22978.
  31. Clarke SF, Murphy EF, O'Sullivan O, et al. Targeting the microbiota to address diet-induced obesity: a time dependent challenge. PloS One 2013;8:e65790.
  32. Wang K-L, Cheng H-M, Chuang S-Y, et al. Central or peripheral systolic or pulse pressure: which best relates to target-organs and future mortality? J Hypertension 2009;27:461.
  33. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure the strong heart study. Hypertension 2007;50:197-203.
  34. Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 2010;26:631-640.

Authors
Boutagy, N. E., Neilson, A. P., Osterberg, K. L., Smithson, A. T., Englund, T. R., Davy, B. M., Hulver, M. W., & Davy, K. P.
Affiliations
Virginia Tech (US)
Corresponding author
Davy, Kevin P.
ORCID
Venue
Obesity
Publisher
Wiley
Published
2015-10-14
Volume
23
Issue
12
Pages
2357-2363
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1002/oby.21212
OpenAlex
W1903768306
Cited by
127
References
39
Citations by year
2026: 2 · 2025: 11 · 2024: 12 · 2023: 8 · 2022: 16 · 2021: 21 · 2020: 13 · 2019: 17 · 2018: 16 · 2017: 6 · 2016: 4 · 2015: 1
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
probiotics, VSL#3, trimethylamine N-oxide, high-fat diet, hypercaloric diet, L-carnitine, choline, betaine, gut microbiota, dietary fat
MeSH terms
Adolescent, Adult, Betaine, Carnitine, Choline, Fasting, Humans, Male, Methylamines, Dietary Supplements, Probiotics, Tandem Mass Spectrometry, Young Adult, Diet, High-Fat

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