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New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study


Background and aims

сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity.


70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic “Symbiter”, containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera).


Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20–70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels – IL-1β (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-β (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains.


Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.

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  1. World Health Organization. Obesity and overweight. Fact sheet N 311,, 2015.

  2. Dee A, Kearns K, O’Neill C, Sharp L, Staines A, O’Dwyer V, et al. The direct and indirect costs of both overweight and obesity: a systematic review. BMC Res Notes. 2014;7:242.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Melvin A, O'Rahilly S, Savage DB. Genetic syndromes of severe insulin resistance. Curr Opin Genet Dev. 2018;50:60–7.

    CAS  Article  PubMed  Google Scholar 

  4. Mykhalchyshyn G, Kobyliak N, Bodnar P. Diagnostic accuracy of acyl-ghrelin and it association with non-alcoholic fatty liver disease in type 2 diabetic patients. J Diabetes Metab Disord. 2015;14:44.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Kyriachenko Y, Falalyeyeva T, Korotkyi O, Molochek N, Kobyliak N. Crosstalk between gut microbiota and antidiabetic drug action. World J Diabetes. 2019;10:154–68.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.

    CAS  Article  PubMed  Google Scholar 

  7. Kobyliak N, Falalyeyeva T, Boyko N, Tsyryuk O, Beregova T, Ostapchenko L. Probiotics and nutraceuticals as a new frontier in obesity prevention and management. Diabetes Res Clin Pract. 2018;141:190–9.

    CAS  Article  PubMed  Google Scholar 

  8. Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterol. 2013;145:396–406.

    CAS  Article  Google Scholar 

  9. Puddu A, Sanguineti R, Montecucco F, Viviani GL. Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes. Mediat Inflamm. 2014;2014:162021.

    CAS  Article  Google Scholar 

  10. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116:3015–25.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Renga B, Mencarelli A, Vavassori P, Brancaleone V, Fiorucci S. The bile acid sensor FXR regulates insulin transcription and secretion. Biochim Biophys Acta. 1802;2010:363–72.

    CAS  Article  Google Scholar 

  12. Ding L, Yang L, Wang Z, Huang W. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B. 2015;5:135–44.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document: the international scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2017;14:491–502.

    Article  Google Scholar 

  14. Kobyliak N, Abenavoli L, Falalyeyeva T, Mykhalchyshyn G, Boccuto L, Kononenko L, et al. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Minerva Med. 2018;109:418–28.

    Article  PubMed  Google Scholar 

  15. Kobyliak N, Abenavoli L, Mykhalchyshyn G, Falalyeyeva T, Tsyryuk O, Kononenko L, et al. Probiotics and smectite absorbent gel formulation reduce liver stiffness, transaminases and cytokine levels in NAFLD associated with type 2 diabetes: a randomized clinical study. Clinical Diabetology. 2019;8:205–14.

    CAS  Article  Google Scholar 

  16. Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: randomized clinical trial. Diabetes Metab Syndr. 2018;12:617–24.

    Article  PubMed  Google Scholar 

  17. Cani PD, Van Hul M. Novel opportunities for next-generation probiotics targeting metabolic syndrome. Curr Opin Biotechnol. 2015;32:21–7.

    CAS  Article  PubMed  Google Scholar 

  18. Wu TR, Lin CS, Chang CJ, Lin TL, Martel J, Ko YF, et al. Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut. 2019;68:248–62.

    CAS  Article  PubMed  Google Scholar 

  19. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol. 2017;8:1765.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kobyliak N, Falalyeyeva T, Beregova T, Spivak M. Probiotics for experimental obesity prevention: focus on strain dependence and viability of composition. Endokrynol Pol. 2017;68:659–67.

    CAS  Article  PubMed  Google Scholar 

  21. Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164:719–21.

    CAS  Article  PubMed  Google Scholar 

  22. Kobyliak N, Falalyeyeva T, Bodnar P, Tl B. Probiotics supplemented with Omega-3 fatty acids are more effective for hepatic Steatosis reduction in an animal model of obesity. Probiotics Antimicrob Proteins. 2017;9:123–30.

    CAS  Article  PubMed  Google Scholar 

  23. Kondro M, Mykhalchyshyn G, Bodnar P, Kobyliak N, Falalyeyeva T. Metabolic profile and morpho-functional state of the liver in rats with glutamate-induced obesity. Curr. Issues Pharm. Med Sci. 2013;26:379–81.

    Article  Google Scholar 

  24. Kobyliak N, Abenavoli L, Falalyeyeva T, Virchenko O, Natalia B, Beregova T, et al. Prevention of NAFLD development in rats with obesity via the improvement of pro/antioxidant state by cerium dioxide nanoparticles. Clujul Med. 2016;89:229–35.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kobyliak N, Abenavoli L, Falalyeyeva T, Beregova T. Efficacy of probiotics and Smectite in rats with non-alcoholic fatty liver disease. Ann Hepatol. 2018;17:153–61.

    CAS  Article  PubMed  Google Scholar 

  26. Novelli ELB, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, et al. Anthropometrical parameters and markers of obesity in rats. Lab Anim. 2007;41:111–9.

    CAS  Article  Google Scholar 

  27. Vogeser M, Konig D, Frey I, Predel HG, Parhofer KG, Berg A. Fasting serum insulin and the homeostasis model of insulin resistance (HOMA-IR) in the monitoring of lifestyle interventions in obese persons. Clin Biochem. 2007;40:964–8.

    CAS  Article  Google Scholar 

  28. Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T. The neuropeptide Y/agouti generated protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A. 1998;95:15043–8.

    CAS  Article  Google Scholar 

  29. Dawson R, Pelleymounter MA, Millard WJ, Liu S, Eppler B. Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage. Am J Phys. 1997;273:202–6.

    Google Scholar 

  30. Matysková R, Maletínská L, Maixnerová J, Pirník Z, Kiss A, Zelezná B. Comparison of the obesity phenotypes related to monosodium glutamate effect on arcuate nucleus and/or the high fat diet feeding in C57BL/6 and NMRI mice. Physiol Res. 2008;57:727–34.

    PubMed  Google Scholar 

  31. Li X, Wang E, Yin B, Fang D, Chen P, Wang G, Zhao J et al. Effects of lactobacillus casei ccfm419 on insulin resistance and gut microbiota in type 2 diabetic mice. Benef. Microbes 2017; 8: 421–432. doi: doi: 10.5603/EP.a2017.0055.

  32. Yadav H, Jain S, Sinha PR. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition. 2007;23:62–8.

    Article  PubMed  Google Scholar 

  33. Park DY, Ahn YT, Park SH, Huh CS, Yoo SRYR, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One. 2013;8:e59470.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Carreras NL, Martorell P, Chenoll E, Genovés S, Ramón D, Aleixandre A. Anti-obesity properties of the strain Bifidobacterium animalis subsp. lactis CECT 8145 in Zücker fatty rats. Benef Microbes. 2018;9:629–41.

    CAS  Article  PubMed  Google Scholar 

  35. Roselli M, Finamore A, Brasili E, Rami R, Nobili F, Orsi C, et al. Beneficial effects of a selected probiotic mixture administered to high fat-fed mice before and after the development of obesity. J Funct Foods. 2018;45:321–9.

    CAS  Article  Google Scholar 

  36. Alard J, Lehrter V, Rhimi M, Mangin I, Peucelle V, Abraham AL, et al. Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota. Environ Microbiol. 2016;18:1484–97.

    CAS  Article  PubMed  Google Scholar 

  37. Holowacz S, Guigné C, Chêne G, Mouysset S, Guilbot A, Seyrig C, et al. A multispecies Lactobacillus- and Bifidobacterium-containing probiotic mixture attenuates body weight gain and insulin resistance after a short-term challenge with a high-fat diet. Pharma Nutrition. 2015;3:101–7.

    CAS  Article  Google Scholar 

  38. Karimi G, Jamaluddin R, Mohtarrudin N, Ahmad Z, Khazaai H, Parvaneh M. Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity. Nutr Metab Cardiovasc Dis. 2017;27:910–8.

    CAS  Article  PubMed  Google Scholar 

  39. Hsieh FC, Lan CC, Huang TY, Chen KW, Chai CY, Chen WT, et al. Heat-killed and live Lactobacillus reuteri GMNL-263 exhibit similar effects on improving metabolic functions in high-fat diet-induced obese rats. Food Funct. 2016;7:2374–88.

    CAS  Article  PubMed  Google Scholar 

  40. Kikuchi K, Ben Othman M, Sakamoto K. Sterilized bifidobacteria suppressed fat accumulation and blood glucose level. Biochem Biophys Res Commun. 2018;501:1041–7.

    CAS  Article  PubMed  Google Scholar 

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The authors express their sincere thanks to Dr. Yankovsky Dmitro Stanislavovych for the help, advice and financial support of this work.

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Correspondence to Nazarii Kobyliak.

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Kobyliak, N., Falalyeyeva, T., Tsyryuk, O. et al. New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study. J Diabetes Metab Disord 19, 289–296 (2020).

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  • Obesity
  • Insulin resistance
  • Lyophilized and alive probiotic strains
  • Lactobacillus
  • Bifidobacterium
  • Multistrain probiotics