Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Bariatric Surgery

Effect of probiotic supplementation on plasma metabolite profile after Roux-Y gastric bypass: a prospective, randomized, double-blind, placebo-controlled clinical trial

Abstract

Background/objective

There is evidence that metabolic profile changes after Roux-Y gastric bypass (RYGB), especially due to modifications in the gastrointestinal tract. In addition, previous studies have suggested that probiotics can modify the microbiome and produce metabolites important for metabolic health maintenance. In this sense, the aim of this study was to verify the influence of probiotic supplementation on the plasma metabolite profile after RYGB.

Methods

This was a randomized, double-blind, placebo-controlled clinical trial conducted with 31 patients subjected to RYGB surgery, randomized in probiotic group that was supplemented with a probiotic supplement (FloraVantage®) for 3 months after surgery or a placebo group. Plasma metabonomics was performed using nuclear magnetic resonance (NMR) at the preoperative period (T0) and at 45–50 days (T1) and 90–95 days (T2) during the postoperative period/intervention.

Results

Reductions in trimethylamine-N-oxide (TMAO) and alanine were observed in both groups, however this reduction was greater in the probiotic group (TMAO 13.82%, p = 0.01 and alanine 14.03%, p = 0.03) at T2. Additionally, β-hydroxybutyrate (BHB) levels increased 10.77% in the probiotic group (p = 0.03) compared to the placebo group at T2.

Conclusion

Supplementation with Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 was able to associate with significant differences in relevant plasma metabolites associated with improved metabolic health.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: First three scores factors from NPLS-DA model showing a clear cluster separation of the placebo (o-red) and probiotic (*-blue) group.
Fig. 2: A representative ¹H NMR spectra (bottom line, red) comparing with the first spectral loading from the NPLS-DA model (top line, black).
Fig. 3: Trajectories of the postprandial states, shown as fold-changes compared to the baseline levels.

Similar content being viewed by others

Data availability

Requests for further information should be directed to the corresponding author.

References

  1. Wang FG, Yan WM, Yan M, Song MM. Outcomes of Mini vs Roux-en-Y gastric bypass: a meta-analysis and systematic review. Int J Surg. 2018;56:7–14.

    Article  PubMed  Google Scholar 

  2. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. Jama. 2004;292:1724–37.

    Article  CAS  PubMed  Google Scholar 

  3. Lager CJ, Esfandiari NH, Luo Y, Subauste AR, Kraftson AT, Brown MB, et al. Metabolic parameters, weight loss, and comorbidities 4 years after Roux-en-Y gastric bypass and sleeve gastrectomy. Obes Surg. 2018;28:3415–23.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377:1143–55.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li JV, Ashrafian H, Bueter M, Kinross J, Sands C, le Roux CW, et al. Metabolic surgery profoundly influences gut microbial–host metabolic cross-talk. Gut. 2011;60:1214–23.

    Article  CAS  PubMed  Google Scholar 

  6. Al Assal K, Prifti E, Belda E, Sala P, Clément K, Dao MC, et al. Gut microbiota profile of obese diabetic women submitted to Roux-en-Y gastric bypass and its association with food intake and postoperative diabetes remission. Nutrients. 2020;12:278.

    Article  CAS  PubMed Central  Google Scholar 

  7. Pajecki D, de Oliveira LC, Sabino EC, de Souza-Basqueira M, Dantas AC, Nunes GC, et al. Changes in the intestinal microbiota of superobese patients after bariatric surgery. Clinics (Sao Paulo). 2019;74:e1198.

    Article  Google Scholar 

  8. Kong LC, Tap J, Aron-Wisnewsky J, Pelloux V, Basdevant A, Bouillot JL, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr. 2013;98:16–24.

    Article  CAS  PubMed  Google Scholar 

  9. Ilhan ZE, DiBaise JK, Isern NG, Hoyt DW, Marcus AK, Kang DW, et al. Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding. ISME J. 2017;11:2047–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Samczuk P, Ciborowski M, Kretowski A. Application of metabolomics to study effects of bariatric surgery. J Diabetes Res. 2018;2018:6270875.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lee ES, Song EJ, Nam YD, Lee SY. Probiotics in human health and disease: from nutribiotics to pharmabiotics. J Microbiol. 2018;56:773–82.

    Article  PubMed  Google Scholar 

  12. Vandenplas Y, Huys G, Daube G. Probiotics: An update. J Pediatr (Rio J). 2015;91:06–21.

    Article  Google Scholar 

  13. Chung HJ, Sim JH, Min TS, Choi HK. Metabolomics and lipidomics approaches in the science of probiotics: a review. J Med Food. 2018;21:1086–95.

    Article  PubMed  Google Scholar 

  14. Seridi L, Leo GC, Dohm GL, Pories WJ, Lenhard J. Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome. PLoS One. 2018;13:e0198156.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jarak I, Pereira SS, Carvalho RA, Oliveira PF, Alves MG, Guimarães M, et al. Gastric bypass with different biliopancreatic limb lengths results in similar post-absorptive metabolomics profiles. Obes Surg. 2020;30:1068–78.

    Article  PubMed  Google Scholar 

  16. Herzog K, Berggren J, Al Majdoub M, Balderas AC, Lindqvist A, Hedenbro J, et al. Metabolic effects of gastric bypass surgery: is it all about calories? Diabetes. 2020;69:2027–35.

    Article  CAS  PubMed  Google Scholar 

  17. Dreyfuss JM, Yuchi Y, Dong X, Efthymiou V, Pan H, Simonson DC, et al. High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control. Nat Commun. 2021;12:6951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jones B, Sands C, Alexiadou K, Minnion J, Tharakan G, Behary P, et al. The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction. J Clin Endocrinol Metab. 2022;107:e767–e782.

    Article  PubMed  Google Scholar 

  19. Greenstein R. Reporting weight loss. Obes Surg. 2007;17:1275.

    Article  PubMed  Google Scholar 

  20. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, et al. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc. 2007;2:2692–703.

    Article  CAS  PubMed  Google Scholar 

  21. Foxall PJ, Spraul M, Farrant RD, Lindon LC, Neild GH, Nicholson JK. 750 MHz 1H-NMR spectroscopy of human blood plasma. J Pharm Biomed Anal. 1993;11:267–76.

    Article  CAS  PubMed  Google Scholar 

  22. Bell JD, Brown JC, Nicholson JK, Sadler PJ. Assignment of resonances for ‘acute-phase’ glycoproteins in high resolution proton NMR spectra of human blood plasma. FEBS Lett. 1987;215:311–5.

    Article  CAS  PubMed  Google Scholar 

  23. Fan TW. Metabolite profiling by one-and two-dimensional NMR analysis of complex mixtures. Progress in nuclear magnetic resonance spectroscopy. 1996;28:161–219.

    Article  CAS  Google Scholar 

  24. R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. Available from: http://www.r-project.org/index.html

  25. Savorani F, Tomasi G, Engelsen SB. icoshift: A versatile tool for the rapid alignment of 1D NMR spectra. J Magn Reson. 2010;202:190–202.

    Article  CAS  PubMed  Google Scholar 

  26. Andersson CA, Bro R. The N-way toolbox for MATLAB. Chemometrics Intelligent Lab Syst. 2000;52:1–4.

    Article  CAS  Google Scholar 

  27. Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery–induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Murphy R, Tsai P, Jüllig M, Liu A, Plank L, Booth M. Differential changes in gut microbiota after gastric bypass and sleeve gastrectomy bariatric surgery vary according to diabetes remission. Obes Surg. 2017;27:917–25.

    Article  PubMed  Google Scholar 

  29. Ramos MRZ, de Oliveira Carlos L, Wagner NRF, Felicidade I, da Cruz MR, Taconeli CA, et al. Effects of Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 supplementation on nutritional and metabolic parameters in the early postoperative period after Roux-en-Y Gastric Bypass: a randomized, double-blind, placebo-controlled trial. Obes Surg. 2021;31:2105–14.

    Article  PubMed  Google Scholar 

  30. Wagner NRF, Ramos MRZ, de Oliveira Carlos L, da Cruz MRR, Taconeli CA, Filho AJB, et al. Effects of probiotics supplementation on gastrointestinal symptoms and SIBO after Roux-en-Y Gastric Bypass: a prospective, randomized, double-blind, placebo-controlled trial. Obes Surg. 2021;31:143–50.

    Article  PubMed  Google Scholar 

  31. Carlos LO, Ramos MRZ, Wagner NRF, Freitas LAC, Felicidade I, Campos ACL. Probiotic supplementation attenuates binge eating and food addiction 1 year after Roux-en-Y Gastric Bypass: a randomized, double-blind, placebo-controlled trial. Arq Bras Cir Dig. 2022;35:e1659.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Cornejo-Pareja I, Clemente-Postigo M, Tinahones FJ. Metabolic and endocrine consequences of bariatric surgery. Front Endocrinol (Lausanne). 2019;10:626.

    Article  Google Scholar 

  33. Clemente-Postigo M, del Mar Roca-Rodriguez M, Camargo A, Ocaña-Wilhelmi L, Cardona F, Tinahones FJ. Lipopolysaccharide and lipopolysaccharide-binding protein levels and their relationship to early metabolic improvement after bariatric surgery. Surg Obes Relat Dis. 2015;11:933–9.

    Article  PubMed  Google Scholar 

  34. Ashrafian H, le Roux CW. Metabolic surgery and gut hormones–a review of bariatric entero-humoral modulation. Physiol Behav. 2009;97:620–31.

    Article  CAS  PubMed  Google Scholar 

  35. Haluzík M, Kratochvílová H, Haluzíková D, Mráz M. Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions. J Endocrinol. 2018;237:R1–R17.

    Article  PubMed  Google Scholar 

  36. Lips MA, Van Klinken JB, van Harmelen V, Dharuri HK, AC’t Hoen P, Laros JF, et al. Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes. Diabetes care. 2014;37:3150–6.

    Article  CAS  PubMed  Google Scholar 

  37. Dharuri H, AC’t Hoen P, van Klinken JB, Henneman P, Laros JF, Lips MA, et al. Downregulation of the acetyl-CoA metabolic network in adipose tissue of obese diabetic individuals and recovery after weight loss. Diabetologia. 2014;57:2384–92.

    Article  CAS  PubMed  Google Scholar 

  38. Lopes TI, Geloneze B, Pareja JC, Calixto AR, Ferreira MM, Marsaioli AJ. Blood metabolome changes before and after bariatric surgery: A 1H NMR-based clinical investigation. OMICS. 2015;19:318–27.

    Article  CAS  PubMed  Google Scholar 

  39. Wijayatunga NN, Sams VG, Dawson JA, Mancini ML, Mancini GJ, Moustaid‐Moussa N. Roux‐en‐Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev. 2018;34:e3045.

    Article  PubMed  PubMed Central  Google Scholar 

  40. She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab. 2007;293:E1552–63.

    Article  CAS  PubMed  Google Scholar 

  41. Juraschek SP, Shantha GP, Chu AY, Miller ER III, Guallar E, Hoogeveen RC, et al. Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study. PloS One. 2013;8:e55113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen YD, Varasteh BB, Reaven GM. Plasma lactate concentration in obesity and type 2 diabetes. Diabete Metab. 1993;19:348–54.

    CAS  PubMed  Google Scholar 

  43. Berggren JR, Boyle KE, Chapman WH, Houmard JA. Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise. Am J Physiol Endocrinol Metab. 2008;294:E726–32.

    Article  CAS  PubMed  Google Scholar 

  44. Jones TE, Pories WJ, Houmard JA, Tanner CJ, Zheng D, Zou K, et al. Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome. Surgery. 2019;166:861–6.

    Article  PubMed  Google Scholar 

  45. Houmard JA, Pories WJ, Dohm GL. Is there a metabolic program in the skeletal muscle of obese individuals? J Obes. 2011;2011:250496.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Fernández M, Zúñiga M. Amino acid catabolic pathways of lactic acid bacteria. Crit Rev Microbiol. 2006;32:155–83.

    Article  PubMed  Google Scholar 

  47. Vieco-Saiz N, Belguesmia Y, Raspoet R, Auclair E, Gancel F, Kempf I, et al. Benefits and inputs from lactic acid bacteria and their bacteriocins as alternatives to antibiotic growth promoters during food-animal production. Front Microbiol. 2019;10:57.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Patrone V, Vajana E, Minuti A, Callegari ML, Federico A, Loguercio C, et al. Postoperative changes in fecal bacterial communities and fermentation products in obese patients undergoing bilio-intestinal bypass. Front Microbiol. 2016;7:200.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Brinkworth GD, Noakes M, Clifton PM, Bird AR. Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Br J Nutr. 2009;101:1493–502.

    Article  CAS  PubMed  Google Scholar 

  50. Wang L, Zhang J, Guo Z, Kwok L, Ma C, Zhang W, et al. Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota, SIgA, SCFAs, and TBAs of adults of different ages. Nutrition. 2014;30:776–83.

    Article  CAS  PubMed  Google Scholar 

  51. Pérez-Burillo S, Pastoriza S, Gironés A, Avellaneda A, Francino MP, Rufián-Henares JA. Potential probiotic salami with dietary fiber modulates metabolism and gut microbiota in a human intervention study. J Functional Foods. 2020;66:103790.

    Article  Google Scholar 

  52. Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611.

    Article  CAS  PubMed  Google Scholar 

  53. Dehghan P, Farhangi MA, Nikniaz L, Nikniaz Z, Asghari‐Jafarabadi M. Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose‐response meta‐analysis. Obes Rev. 2020;21:e12993.

    Article  CAS  PubMed  Google Scholar 

  54. Gruppen EG, Garcia E, Connelly MA, Jeyarajah EJ, Otvos JD, Bakker SJ, et al. TMAO is associated with mortality: impact of modestly impaired renal function. Sci Rep. 2017;7:13781.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Haghikia A, Li XS, Liman TG, Bledau N, Schmidt D, Zimmermann F, et al. Gut microbiota–dependent trimethylamine N-oxide predicts risk of cardiovascular events in patients with stroke and is related to proinflammatory monocytes. Arterioscler Thromb Vasc Biol. 2018;38:2225–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Senthong V, Wang Z, Fan Y, Wu Y, Hazen SL, Tang WW. Trimethylamine N‐oxide and mortality risk in patients with peripheral artery disease. J Am Heart Assoc. 2016;5:e004237.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Din AU, Hassan A, Zhu Y, Yin T, Gregersen H, Wang G. Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Appl Microbiol Biotechnol. 2019;103:9217–28.

    Article  CAS  PubMed  Google Scholar 

  58. Kalani M, Hodjati H, Khanian MS, Doroudchi M. Lactobacillus acidophilus increases the anti-apoptotic micro RNA-21 and decreases the pro-inflammatory micro RNA-155 in the LPS-treated human endothelial cells. Probiotics Antimicrob Proteins. 2016;8:61–72.

    Article  CAS  PubMed  Google Scholar 

  59. Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles J. Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest. 1989;83:1168–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Boden G. Obesity and free fatty acids. Endocrinol Metab Clin North Am. 2008;37:635–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta‐cell dysfunction. Eur J Clin Invest. 2002;32:14–23.

    Article  CAS  PubMed  Google Scholar 

  62. Kullberg J, Sundbom M, Haenni A, Freden S, Johansson L, Börnert P, et al. Gastric bypass promotes more lipid mobilization than a similar weight loss induced by low-calorie diet. J Obes. 2011;2011:959601.

    Article  PubMed  Google Scholar 

  63. Jacobsen SH, Bojsen-Møller KN, Dirksen C, Jørgensen NB, Clausen TR, Wulff BS, et al. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals. Diabetologia. 2013;56:2250–4.

    Article  CAS  PubMed  Google Scholar 

  64. Klein S, Mittendorfer B, Eagon JC, Patterson B, Grant L, Feirt N, et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology. 2006;130:1564–72.

    Article  CAS  PubMed  Google Scholar 

  65. Hansen M, Lund MT, Gregers E, Kraunsøe R, Van Hall G, Helge JW, et al. Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB. Obesity (Silver Spring). 2015;23:2022–9.

    Article  CAS  Google Scholar 

  66. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. The Lancet. 1963;281:785–9.

    Article  Google Scholar 

  67. Lopes TI, Geloneze B, Pareja JC, Calixto AR, Ferreira MM, Marsaioli AJ. “Omics” prospective monitoring of bariatric surgery: Roux-en-Y gastric bypass outcomes using mixed-meal tolerance test and time-resolved 1H NMR-based metabolomics. OMICS. 2016;20:415–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kim YA, Keogh JB, Clifton PM. Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutr Res Rev. 2018;31:35–51.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research received financial support from the CAPES (Coordination for the Improvement of Higher Education Personnel). CAPES had no influence on the writing, submission, or any other part of research formulation.

Author information

Authors and Affiliations

Authors

Contributions

MRZR, LCO, NRFW, IF, MRRC, and ACLC contributed to the conception and design of the study. MRZR, LCO, NRFW were responsible for data collect. MRZR, IF, FCHB, TIBL, MSM, LRR, JVZ, FCMJ, and ACLC were responsible for the analysis, and/or interpretation and discussion of the data. LVAL was responsible for the graphical abstract. MRZR and FCHB submitted the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ingrid Felicidade.

Ethics declarations

Competing interests

The authors declare that they have no conflict of interest. The probiotics were donated by Bariatric Advantage (Aliso Viejo, California, United States) and placebo and glucose by Dermatologica Pharmacy (Curitiba, Paraná, Brazil). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Ethics approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Research Ethics Committee of the Pontifical Catholic University of Paraná (PUCPR) (n° 4.252.808) and was registered in the Brazilian Clinical Trials Registry - REBEC (n°RBR-4x3gqp)

Informed consent

Informed consent was obtained from all subjects involved in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramos, M.R.Z., Felicidade, I., de Oliveira Carlos, L. et al. Effect of probiotic supplementation on plasma metabolite profile after Roux-Y gastric bypass: a prospective, randomized, double-blind, placebo-controlled clinical trial. Int J Obes 46, 2006–2012 (2022). https://doi.org/10.1038/s41366-022-01213-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-022-01213-0

This article is cited by

Search

Quick links