Skip to main content

Advertisement

SpringerLink
Log in

Effect of multi-strain probiotics (multi-strain microbial cell preparation) on glycemic control and other diabetes-related outcomes in people with type 2 diabetes: a randomized controlled trial

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Aim

Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing. However, the effect of multi-strain probiotics in people with type 2 diabetes remains unclear. This study investigated the effect of multi-strain microbial cell preparation—also refers to multi-strain probiotics—on glycemic control and other diabetes-related outcomes in people with type 2 diabetes.

Design

A randomized, double-blind, parallel-group, controlled clinical trial.

Setting

Diabetes clinic of a teaching hospital in Kuala Lumpur, Malaysia.

Participants

A total of 136 participants with type 2 diabetes, aged 30–70 years, were recruited and randomly assigned to receive either probiotics (n = 68) or placebo (n = 68) for 12 weeks.

Outcomes

Primary outcomes were glycemic control-related parameters, and secondary outcomes were anthropomorphic variables, lipid profile, blood pressure and high-sensitivity C-reactive protein. The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract.

Statistical analysis

Intention-to-treat (ITT) analysis was performed on all participants, while per-protocol (PP) analysis was performed on those participants who had successfully completed the trial with good compliance rate.

Results

With respect to primary outcomes, glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis (p < 0.05, small effect size of 0.050), while these changes were not significant in ITT analysis. Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis. These changes were significant between groups at both analyses (p < 0.05, medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis). Secondary outcomes did not change significantly. Probiotics successfully passed through the gastrointestinal tract.

Conclusion

Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Guariguata L, Whiting DR, Hambleton I et al (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149. doi:10.1016/j.diabres.2013.11.002

    Article  CAS  Google Scholar 

  2. Wan Nazaimoon WM, Md Isa SH, Wan Mohamad WB et al (2013) Prevalence of diabetes in Malaysia and usefulness of HbA1c as a diagnostic criterion. Diabet Med 30:825–828. doi:10.1111/dme.12161

    Article  CAS  Google Scholar 

  3. Firouzi S, Barakatun-Nisak MY, Azmi KN (2015) Nutritional status, glycemic control and its associated risk factors among a sample of type 2 diabetic individuals, a pilot study. J Res Med Sci 20:40–46

    CAS  Google Scholar 

  4. Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH (2013) The influence of diet on the gut microbiota. Pharmacol Res 69(1):52–60. doi:10.1016/j.phrs.2012.10.020

    Article  CAS  Google Scholar 

  5. Musso G, Gambino R, Cassader M (2010) Obesity, diabetes, and gut microbiota. The hygiene hypothesis expanded? Diabetes Care 33:2277–2284

    Article  Google Scholar 

  6. Larsen N, Vogensen FK, van den Berg FWJ et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5:e9085

    Article  Google Scholar 

  7. de Kort S, Keszthelyi D, Masclee AAM (2011) Leaky gut and diabetes mellitus: What is the link? Obes Rev 12:449–458. doi:10.1111/j.1467-789X.2010.00845.x

    Article  Google Scholar 

  8. FAO/WHO (2002) WHO|guidelines for the evaluation of probiotics in food: joint FAO/WHO working group meeting, London Ontario, Canada, 30 April–1 May 2002. World Health Organization, London Ontario, Canada

  9. Firouzi S, Barakatun-Nisak MY, Ismail A et al (2013) Role of probiotics in modulating glucose homeostasis: evidence from animal and human studies. Int J Food Sci Nutr 64:780–786. doi:10.3109/09637486.2013.775227

    Article  CAS  Google Scholar 

  10. Ejtahed HS, Mohtadi Nia J, Homayouni Rad A et al (2011) The effects of probiotic and conventional yoghurt on diabetes markers and insulin resistance in type 2 diabetic patients: a randomized controlled clinical trial. Iran J Endocrinol Metab 13:1–8

    Google Scholar 

  11. Mazloom Z, Yousefinejad A, Dabbaghmanesh MH (2013) Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci 38:38–43

    Google Scholar 

  12. Asemi Z, Zare Z, Shakeri H et al (2013) Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann Nutr Metab 63:1–9

    Article  CAS  Google Scholar 

  13. Le Chatelier E, Nielsen T, Qin J et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546. doi:10.1038/nature12506

    Article  Google Scholar 

  14. Park S, Bae J-H (2015) Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res 35:566–575. doi:10.1016/j.nutres.2015.05.008

    Article  CAS  Google Scholar 

  15. Naito E, Yoshida Y, Makino K et al (2011) Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice. J Appl Microbiol 110:650–657

    Article  CAS  Google Scholar 

  16. Chen JJ, Wang R, Li X (2011) Bifidobacterium longum supplementation improved high-fat-fed-induced metabolic syndrome and promoted intestinal Reg I gene expression. Exp Biol Med 236:823–831

    Article  CAS  Google Scholar 

  17. Jauhiainen T, Collin M, Narva M et al (2005) Effect of long-term intake of milk peptides and minerals on blood pressure and arterial function in spontaneously hypertensive rats. Milchwissenschaft-Milk Sci Int 60:358–362

    CAS  Google Scholar 

  18. Agerholm-Larsen L, Raben A, Haulrik N et al (2000) Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur J Clin Nutr 54:288–297

    Article  CAS  Google Scholar 

  19. Guo Z, Liu XM, Zhang QX et al (2011) Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis 21:844–850

    Article  CAS  Google Scholar 

  20. Malaysian Dietitians’ Association (2013) Clinical Practice Guideline, Medical nutrition therapy guideline for type 2 diabetes Mellitus. Ministry of Health, Kuala Lumpur, Malaysia

  21. Cole HS, Camerini-Davalos RA (1970) Diet therapy of diabetes mellitus. Med Clin North Am 54:1577–1587

    CAS  Google Scholar 

  22. Krueger KP, Felkey BG, Berger BA (2003) Improving adherence and persistence: a review and assessment of interventions and description of steps toward a national adherence initiative. J Am Pharm Assoc 43:668–679

    Article  Google Scholar 

  23. WHO expert consultation (2000) Obesity: preventing and managing the global epidemic Report of a WHO Consultation (WHO Technical Report Series 894). Geneva

  24. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  Google Scholar 

  25. Katz A, Nambi SS, Mather K et al (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410

    Article  CAS  Google Scholar 

  26. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  Google Scholar 

  27. Chu AHY, Moy FM (2012) Reliability and validity of the malay international physical activity questionnaire (IPAQ-M) among a malay population in Malaysia. Asia Pac J Public Health 27:NP2381–NP2389

    Article  Google Scholar 

  28. De Vrese M, Winkler P, Rautenberg P et al (2005) Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin Nutr 24:481–491. doi:10.1016/j.clnu.2005.02.006

    Article  Google Scholar 

  29. Albertini B, Vitali B, Passerini N et al (2010) Development of microparticulate systems for intestinal delivery of Lactobacillus acidophilus and Bifidobacterium lactis. Eur J Pharm Sci 40:359–366. doi:10.1016/j.ejps.2010.04.011

    Article  CAS  Google Scholar 

  30. Haarman M, Knol J (2006) Quantitative real-time PCR analysis of fecal Lactobacillus species in infants receiving a prebiotic infant formula. Appl Environ Microbiol 72:2359–2365. doi:10.1128/AEM.72.4.2359

    Article  CAS  Google Scholar 

  31. Andreasen AS, Larsen N, Pedersen-Skovsgaard T et al (2010) Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br J Nutr 104:1831–1838

    Article  CAS  Google Scholar 

  32. Laitinen K, Poussa T, Isolauri E (2009) Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial. Br J Nutr 101:1679–1687

    Article  CAS  Google Scholar 

  33. Ivey KL, Hodgson JM, Kerr DA et al (2014) The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial. Eur J Clin Nutr 68:447–452. doi:10.1038/ejcn.2013.294

    Article  CAS  Google Scholar 

  34. Gobel RJ, Larsen N, Jakobsen M et al (2012) Probiotics to obese adolescents; RCT examining the effects on inflammation and metabolic syndrome. J Pediatr Gastroenterol Nutr 5:673–678

    Article  Google Scholar 

  35. Al-Salami H, Butt G, Fawcett JP et al (2008) Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats. Eur J Drug Metab Pharmacokinet 33:101–106

    Article  CAS  Google Scholar 

  36. Zhou J, Martin RJ, Tulley RT et al (2008) Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Metab 295:E1160–E1166

    CAS  Google Scholar 

  37. Jensen TE, Richter EA (2012) Regulation of glucose and glycogen metabolism during and after exercise. J Physiol 590:1069–1076. doi:10.1113/jphysiol.2011.224972

    Article  CAS  Google Scholar 

  38. Munsters MJM, Saris WHM (2012) Effects of meal frequency on metabolic profiles and substrate partitioning in lean healthy males. PLoS ONE 7:e38632. doi:10.1371/journal.pone.0038632

    Article  CAS  Google Scholar 

  39. Morton GJ, Schwartz MW (2011) Leptin and the central nervous system control of glucose metabolism. Physiol Rev 91:389–411. doi:10.1152/physrev.00007.2010

    Article  CAS  Google Scholar 

  40. Burcelin R, Serino M, Chabo C et al (2011) Gut microbiota and diabetes: from pathogenesis to therapeutic perspective. Acta Diabetol 48(4):257–273

    Article  Google Scholar 

  41. Pi-Sunyer FX (2005) Weight loss in type 2 diabetic patients. Diabetes Care 28:1526–1527

    Article  Google Scholar 

  42. Pereira DIA, Gibson GR (2002) Effects of consumption of probiotics and prebiotics on serum lipid levels in humans. Crit Rev Biochem Mol Biol 37:259–281. doi:10.1080/10409230290771519

    Article  CAS  Google Scholar 

  43. Ejtahed HS, Mohtadi Nia J, Homayouni Rad A et al (2011) Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J Dairy Sci 94:3288–3294

    Article  CAS  Google Scholar 

  44. Sadrzadeh-Yeganeh H, Elmadfa I, Djazayery A et al (2010) The effects of probiotic and conventional yoghurt on lipid profile in women. Br J Nutr 103:1778–1783. doi:10.1017/S0007114509993801

    Article  CAS  Google Scholar 

  45. Laakso M, Sarlund H, Salonen R et al (1991) Asymptomatic atherosclerosis and insulin resistance. Arterioscler Thromb Vasc Biol 11:1068–1076. doi:10.1161/01.ATV.11.4.1068

    Article  CAS  Google Scholar 

  46. Chew BH, Ismail M, Lee PY et al (2012) Determinants of uncontrolled dyslipidaemia among adult type 2 diabetes in Malaysia: the Malaysian Diabetes Registry 2009. Diabetes Res Clin Pract 96:339–347. doi:10.1016/j.diabres.2012.01.017

    Article  Google Scholar 

  47. Ooi LG, Liong MT (2010) Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. Int J Mol Sci 11:2499–2522. doi:10.3390/ijms11062499

    Article  CAS  Google Scholar 

  48. Seppo L, Jauhiainen T, Poussa T, Korpela R (2003) A fermented milk high in bioactive peptides has a blood pressure–lowering effect in hypertensive subjects. Am J Clin Nutr 77:326

    CAS  Google Scholar 

  49. Ansell BJ, Watson KE, Weiss RE, Fonarow GC (2003) hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation. Heart Dis 5:2–7. doi:10.1097/01.HDX.0000050407.62572.DE

    Article  CAS  Google Scholar 

  50. Ridker PM, Danielson E, Fonseca FA et al (2009) Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 373:1175–1182. doi:10.1016/S0140-6736(09)60447-5

    Article  CAS  Google Scholar 

  51. WHO expert consultation (2004) BMI classification. http://apps.who.int/bmi/index.jsp?introPage=intro_3.html

  52. Turnbaugh PJ, Hamady M, Yatsunenko T et al (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484. doi:10.1038/nature07540

    Article  CAS  Google Scholar 

  53. Million M, Angelakis E, Maraninchi M et al (2013) Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes 37:1460–1466. doi:10.1038/ijo.2013.20

    Article  CAS  Google Scholar 

  54. Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489:242–249. doi:10.1038/nature11552

    Article  CAS  Google Scholar 

  55. Caricilli AM, Picardi PK, de Abreu LL et al (2011) Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice. PLoS Biol 9:e1001212. doi:10.1371/journal.pbio.1001212

    Article  CAS  Google Scholar 

  56. Singh B, Saxena A (2010) Surrogate markers of insulin resistance: a review. World J Diabetes 1:36–47

    Article  Google Scholar 

  57. Renga B, Mencarelli A, Vavassori P et al (2010) The bile acid sensor FXR regulates insulin transcription and secretion. Biochim Biophys Acta 1802:363–372. doi:10.1016/j.bbadis.2010.01.002

    Article  CAS  Google Scholar 

  58. Ding L, Yang L, Wang Z, Huang W (2015) Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B 5:135–144. doi:10.1016/j.apsb.2015.01.004

    Article  Google Scholar 

  59. Shyangdan DS, Royle P, Clar C et al (2011) Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. doi:10.1002/14651858.CD006423.pub2

    Google Scholar 

  60. Tilg H, Moschen AR (2014) Microbiota and diabetes: an evolving relationship. Gut 63:1513–1521. doi:10.1136/gutjnl-2014-306928

    Article  CAS  Google Scholar 

  61. Puddu A, Sanguineti R, Montecucco F, Viviani GL (2014) Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes. Mediators Inflamm 2014:162021. doi:10.1155/2014/162021

    Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the participants and project partners for their enthusiastic support of the study. We thank Universiti Putra Malaysia and B-Crobes Laboratory Sdn. Bhd. for funding this project.

Financial support

This study was funded by internal grant of Universiti Putra Malaysia and research grant of B-Crobes Laboratory Sdn. Bhd. The supplements were provided by “B-Crobes Laboratory Sdn. Bhd.”

Author’s contribution

The authors’ responsibilities were as follows: SF (PhD student) was involved in study conception, study coordination, study conduct, laboratory testing and analysis, statistical analysis and manuscript writing; HAM critically reviewed the manuscript; AI reviewed the manuscript; NAK was involved in administrative coordination; MY B-N served as principle investigator, was involved in study conception and study coordination and reviewed the manuscript. All authors were responsible for the study design.

Author information

Authors and Affiliations

  1. Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia

    Somayyeh Firouzi, Amin Ismail & Mohd-Yusof Barakatun-Nisak

  2. Department of Social and Preventive Medicine, Faculty of Medicine, Centre for Population Health, University of Malaya, Kuala Lumpur, Malaysia

    Hazreen Abdul Majid

  3. Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Nor Azmi Kamaruddin

Authors
  1. Somayyeh Firouzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hazreen Abdul Majid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amin Ismail
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nor Azmi Kamaruddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohd-Yusof Barakatun-Nisak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohd-Yusof Barakatun-Nisak.

Ethics declarations

Conflict of interest

The authors have nothing to disclose.

Ethical approval

The protocol was approved by the Clinical Research and Ethics Committee of the Universiti Kebangsaan Malaysia Medical Center, conformed to the contents of the 1975 Declaration of Helsinki as revised in 1983, and was registered at the US National Institutes of Health Web site (http://www.clinicaltrials.gov) #NCT01752803.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 250 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Firouzi, S., Majid, H.A., Ismail, A. et al. Effect of multi-strain probiotics (multi-strain microbial cell preparation) on glycemic control and other diabetes-related outcomes in people with type 2 diabetes: a randomized controlled trial. Eur J Nutr 56, 1535–1550 (2017). https://doi.org/10.1007/s00394-016-1199-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-016-1199-8

Keywords

Search

Navigation