Skip to main content
Log in

Probiotics Supplemented with Omega-3 Fatty Acids are More Effective for Hepatic Steatosis Reduction in an Animal Model of Obesity

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Today probiotics have been suggested as a treatment for the prevention of NAFLD. Omega-3 fatty acid supplementation may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function and inflammation. The present study was designed to determine whether probiotics plus omega-3 are superior to probiotics alone on the monosodium glutamate (MSG)-induced NAFLD model in rats. We included 60 rats divided into four groups, 15 animals in each. Rats of group I were intact. Newborn rats of groups II–IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic “Symbiter” containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter-Omega) groups received “Symbiter-Omega” combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1–5 %). In both interventional groups reduction in total NAS score was observed. Supplementation of alive probiotic mixture with omega-3 fatty acids lead to 20 % higher decrease in steatosis score (0.73 ± 0.11 vs 0.93 ± 0.22, p = 0.848) and reduction by 16.6 % of triglycerides content in liver as compared to probiotic alone. Our study demonstrated more pronounced reduction in hepatic steatosis and hepatic lipid accumulation after treatment with combination of alive probiotics and omega-3 as compared to probiotics alone.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Byrne CD, Targher G (2016) EASL–EASD–EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease: is universal screening appropriate? Diabetology 59:141–144. doi:10.1007/s00125-016-3910-y

    Article  Google Scholar 

  2. Kobyliak N, Abenavoli L (2014) The role of liver biopsy to assess non-alcoholic fatty liver disease. Rev Recent Clin Trials 9:159–169

    Article  Google Scholar 

  3. Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285. doi:10.1111/j.1365-2036.2011.04724.x

    Article  CAS  Google Scholar 

  4. Farrell GS, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43(Suppl 1):S99–S112

    Article  CAS  Google Scholar 

  5. Weston SR, Leyden W, Murphy R, Bass NM, Bell BP, Manos MM, Terrault NA (2005) Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 41:372–379

    Article  Google Scholar 

  6. Musso G, Gambino R, Cassader M, Pagano G (2011) Meta-analysis: natural history of nonalcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 43:617–649. doi:10.3109/07853890.2010.518623

    Article  Google Scholar 

  7. Kobyliak N, Virchenko O, Falalyeyeva T (2016) Pathophysiological role of host microbiota in the development of obesity. Nutr J 15:43. doi:10.1186/s12937-016-0166-9

    Article  Google Scholar 

  8. Federico A, Dallio M, Godos J, Loguercio C, Salomone F (2016) Targeting gut-liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence. Transl Res 167:116–124. doi:10.1016/j.trsl.2015.08.002

    Article  CAS  Google Scholar 

  9. Cani PD, Van Hul M (2015) Novel opportunities for next-generation probiotics targeting metabolic syndrome. Curr Opin Biotechnol 32:21–27. doi:10.1016/j.copbio.2014.10.006

    Article  CAS  Google Scholar 

  10. Kobyliak N, Conte C, Cammarota G, Haley AP, Styriak I, Gaspar L, Fusek J, Rodrigo L, Kruzliak P (2016) Probiotics in prevention and treatment of obesity: a critical view. Nutr Metab (Lond) 13:14. doi:10.1186/s12986-016-0067-0

    Article  Google Scholar 

  11. Savcheniuk O, Kobyliak N, Kondro M, Virchenko O, Falalyeyeva T, Beregova T (2014) Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity. BMC Complement Altern Med 14:247. doi:10.1186/1472-6882-14-247

    Article  Google Scholar 

  12. Scorletti E, Byrne CD (2013) Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu Rev Nutr 33:231–248. doi:10.1146/annurev-nutr-071812-161230

    Article  CAS  Google Scholar 

  13. Pettinelli P, Del Pozo T, Araya J, Rodrigo R, Araya AV, Smok G, Csendes A, Gutierrez L, Rojas J, Korn O, Maluenda F, Diaz JC, Rencoret G, Braghetto I, Castillo J, Poniachik J, Videla LA (2009) Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n_3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta 1792(11):1080–1086. doi:10.1016/j.bbadis.2009.08.015

    Article  CAS  Google Scholar 

  14. Parker HM, Johnson NA, Burdon CA, Cohn JS, O’Connor HT, George J (2012) Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 56:944–951. doi:10.1016/j.jhep.2011.08.018

    Article  CAS  Google Scholar 

  15. Zivkovic AM, German JB, Sanyal AJ (2007) Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr 86:285–300

    CAS  Google Scholar 

  16. Kobyliak N, Abenavoli L, Falalyeyeva T, Virchenko O, Natalia B, Beregova T, Bodnar P, Spivak M (2016) Prevention of NAFLD development in rats with obesity via the improvement of pro/antioxidant state by cerium dioxide nanoparticles. Clujul Med 89:229–235. doi:10.15386/cjmed-632

    Article  Google Scholar 

  17. Nakagawa T, Ukai K, Ohyama T, Gomita Y, Okamura H (2000) Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: relationship of antiobesity effect with monoamines. Exp Anim 49:239–249

    Article  CAS  Google Scholar 

  18. Kondro M, Mykhalchyshyn G, Bodnar P, Kobyliak N, Falalyeyeva T (2013) Metabolic profile and morpho-functional state of the liver in rats with glutamate-induced obesity. Curr Issues Pharm Med Sci 26:379–381. doi:10.12923/j.2084-980X/26.4/a.05

    Article  Google Scholar 

  19. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321

    Article  Google Scholar 

  20. Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    CAS  Google Scholar 

  21. Vitetta L, Hall S, Linnane AW (2014) Live probiotic cultures and the gastrointestinal tract: symbiotic preservation of tolerance whilst attenuating pathogenicity. Front Cell Infect Microbiol 4:143. doi:10.3389/fcimb.2014.00143

    Article  Google Scholar 

  22. Kobyliak N, Falalyeyeva T, Virchenko O, Mykhalchyshyn G, Bodnar P, Spivak M, Yankovsky D, Beregova T, Ostapchenko L (2016) Comparative experimental investigation on the efficacy of mono- and multiprobiotic strains in non-alcoholic fatty liver disease prevention. BMC Gastroenterol 16:34. doi:10.1186/s12876-016-0451-2

    Article  Google Scholar 

  23. Mei L, Tang Y, Li M, Yang P, Liu Z, Yuan J, Zheng P (2015) Co-administration of cholesterol-lowering probiotics and anthraquinone from Cassia obtusifolia L. ameliorate non-alcoholic fatty liver. PLoS ONE 10:e0138078. doi:10.1371/journal.pone.0138078

    Article  Google Scholar 

  24. Yoo SR, Kim YJ, Park DY, Jung UJ, Jeon SM, Ahn YT, Huh CS, McGregor R, Choi MS (2013) Probiotics L. plantarum and L. curvatus in combination alter hepatic lipid metabolism and suppress diet-induced obesity. Obesity (Silver Spring) 21:2571–2578. doi:10.1002/oby.20428

    Article  CAS  Google Scholar 

  25. Kim SW, Park KY, Kim B, Kim E, Hyun CK (2013) Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production. Biochem Biophys Res Commun 431:258–263. doi:10.1016/j.bbrc.2012.12.121

    Article  CAS  Google Scholar 

  26. Briskey D, Heritage M, Jaskowski L, Peake J, Gobe G, Subramaniam VN, Crawford D, Campbell C, Vitetta L (2016) Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease. Therap Adv Gastroenterol. doi:10.1177/1756283X16645055

    Google Scholar 

  27. Ritze Y, Bárdos G, Claus A, Ehrmann V, Bergheim I, Schwiertz A, Bischoff SC (2014) Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS ONE 9:e80169. doi:10.1371/journal.pone.0080169

    Article  Google Scholar 

  28. Plaza-Diaz J, Gomez-Llorente C, Abadia-Molina F, Saez-Lara MJ, Campaña-Martin L, Muñoz-Quezada S, Romero F, Gil A, Fontana L (2014) Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats. PLoS ONE 9:e98401. doi:10.1371/journal.pone.0098401

    Article  Google Scholar 

  29. Reichold A, Brenner SA, Spruss A, Förster-Fromme K, Bergheim I, Bischoff SC (2014) Bifidobacterium adolescentis protects from the development of nonalcoholic steatohepatitis in a mouse model. J Nutr Biochem 25:118–125. doi:10.1016/j.jnutbio.2013.09.011

    Article  CAS  Google Scholar 

  30. Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI (2007) n-3 fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-α-dependent manner. Diabetes 56:1034–1041

    Article  CAS  Google Scholar 

  31. Takeuchi Y, Yahagi N, Izumida Y, Nishi M, Kubota M, Teraoka Y, Yamamoto T, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Ohashi K, Osuga J, Gotoda T, Ishibashi S, Itaka K, Kataoka K, Nagai R, Yamada N, Kadowaki T, Shimano H (2010) Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit. J Biol Chem 285:11681–11691. doi:10.1074/jbc.M109.096107

    Article  CAS  Google Scholar 

  32. Opreanu M, Lydic TA, Reid GE, McSorley KM, Esselman WJ, Busik JV (2010) Inhibition of cytokine signaling in human retinal endothelial cells through downregulation of sphingomyelinases by docosahexaenoic acid. Invest Ophthalmol Vis Sci 51:3253–3263. doi:10.1167/iovs.09-4731

    Article  Google Scholar 

  33. Borengasser SJ, Rector RS, Uptergrove GM, Morris EM, Perfield JW 2nd, Booth FW, Fritsche KL, Ibdah JA, Thyfault JP (2012) Exercise and omega-3 polyunsaturated fatty acid supplementation for the treatment of hepatic steatosis in hyperphagic OLETF rats. J Nutr Metab 2012:268680. doi:10.1155/2012/268680

    Article  Google Scholar 

  34. Rajkumar H, Mahmood N, Kumar M, Varikuti SR, Challa HR, Myakala SP (2014) Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators Inflamm 2014:348959. doi:10.1155/2014/348959

    Article  Google Scholar 

Download references

Acknowledgments

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

Authors’ Contribution

Petro Bodnar and Tetyana Beregova conceived and designed the study. Nazarii Kobyliak and Tetyana Falalyeyeva carried out experiments, collected data, analyzed data and wrote the manuscript. All authors have read and approved the final version to be published.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nazarii Kobyliak.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Ethical Approval

This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the general ethical principles of animal experiments, approved by the First National Congress on Bioethics Ukraine (September 2001). The protocol was approved by the Committee on the Ethics of Animal Experiments of the Taras Shevchenko National University of Kyiv (Protocol Number: 17/2015).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kobyliak, N., Falalyeyeva, T., Bodnar, P. et al. Probiotics Supplemented with Omega-3 Fatty Acids are More Effective for Hepatic Steatosis Reduction in an Animal Model of Obesity. Probiotics & Antimicro. Prot. 9, 123–130 (2017). https://doi.org/10.1007/s12602-016-9230-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-016-9230-1

Keywords

Navigation