Amelioration of obesity-related characteristics by a probiotic formulation in a high-fat diet-induced obese rat model

  • Joo-Hyun Shin
  • Myung Hee Nam
  • Hyerim Lee
  • Joong-Su Lee
  • Hojun Kim
  • Myung-Jun Chung
  • Jae-Gu Seo
Original Contribution

Abstract

Purpose

Obesity is a major public health concern. Despite its multi-factorial etiology, alterations in intestinal microbiota and the immune system are frequently observed. We investigated the effect of Duolac Gold (DG), a probiotic formulation containing 2 Lactobacillus strains (L. acidophilus LA1 and L. rharmnosus LR5), 3 Bifidobacterium (B. bifidum BF3, B. lactis BL3, and B. longum BG7), and Streptococcus thermophilus ST3, on morphometric and metabolic parameters, intestinal microbiota, and intestinal immune responses in a high-fat diet (HFD)-induced obese rat model.

Methods

Rats received either a conventional balanced diet or HFD with or without water containing DG for 8 weeks. HFD-induced adiposity, intestinal microbiota, and changes in inflammatory cytokine, chemokine, and metabolite levels in serum were evaluated.

Results

DG administration effectively decreased HFD-induced body weight and modulated morphometric and metabolic parameters. Quantitative analysis of fecal microbiota showed that obese rats given DG exhibited significantly increased levels of Bacteroidetes, Lactobacillus, and Bifidobacterium, with significant decreases in the level of Firmicutes. Serum levels of the inflammatory cytokines and the chemokine were also altered. Serum metabolite analysis revealed that DG administration modulated HFD-induced changes in serum metabolites, including fatty acids (FA), lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylcholine (PC), and triacylglycerol (TAG).

Conclusions

DG administration appears to have the potential to alleviate HDF-induced obesity through the modulation of intestinal microbiota, immune responses, and host metabolism, which supports the use of probiotics to treat obesity.

Keywords

Probiotics High-fat diet Obesity Intestinal microbiota 

Notes

Acknowledgements

This work was financially supported in part by Cell Biotech Co., Ltd., Korea.

Compliance with ethical standards

Conflict of interest

JH.S., J.S.L., M.J.C., and J.G.S. are fully employed by Cell Biotech Co., Ltd., Korea.

Supplementary material

394_2017_1481_MOESM1_ESM.tif (1.4 mb)
Fig. S1Score plots and S plots of orthogonal partial least-squares discriminant analysis (OPLS-DA) in positive (A) and negative (B) modes. To evaluate metabolite mass ions that cause discrimination between ND (open triangle) and HFD (open diamond), the p (corr) value was acquired for each mass ion from the OPLS-DA S-plot (TIFF 1478 kb)

References

  1. 1.
    Janghorbani M, Momeni F, Dehghani M (2012) Hip circumference, height and risk of type 2 diabetes: systematic review and meta-analysis. Obes Rev 13:1172–1181CrossRefGoogle Scholar
  2. 2.
    Jung DH, Kim JY, Kim JK, Koh SB, Park JK, Ahn SV (2014) Relative contribution of obesity and serum adiponectin to the development of hypertension. Diabetes Res Clin Pract 103:51–56CrossRefGoogle Scholar
  3. 3.
    Cani PD, Delzenne NM (2009) The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 15:1546–1558CrossRefGoogle Scholar
  4. 4.
    Moya-Perez A, Romo-Vaquero M, Tomas-Barberan F, Sanz Y, Garcia-Conesa MT (2014) Hepatic molecular responses to Bifidobacterium pseudocatenulatum CECT 7765 in a mouse model of diet-induced obesity. Nutr Metab Cardiovasc Dis 24:57–64CrossRefGoogle Scholar
  5. 5.
    Chen JJ, Wang R, Li XF, Wang RL (2011) Bifidobacterium longum supplementation improved high-fat-fed-induced metabolic syndrome and promoted intestinal Reg I gene expression. Exp Biol Med (Maywood) 236:823–831CrossRefGoogle Scholar
  6. 6.
    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 21:2571–2578CrossRefGoogle Scholar
  7. 7.
    Kang JH, Yun SI, Park HO (2010) Effects of Lactobacillus gasseri BNR17 on body weight and adipose tissue mass in diet-induced overweight rats. J Microbiol 48:712–714CrossRefGoogle Scholar
  8. 8.
    Yoon H, Yoon YS, Kim MS, Chung MJ, Yum DY (2014) A probiotic Preparation duolac-gold ameliorates dextran sulphate sodium-induced mouse colitis by downregulating the expression of IL-6. Toxicol Res 30:27–32CrossRefGoogle Scholar
  9. 9.
    Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG (2014) Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastrol Hepatol 29:52–59CrossRefGoogle Scholar
  10. 10.
    Kwak DS, Jun DW, Seo JG, Chung WS, Park SE, Lee KN, Khalid-Saeed W, Lee HL, Lee OY, Yoon BC, Choi HS (2014) Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease. Eur J Gastrol Hepatol 26:1353–1359Google Scholar
  11. 11.
    Yeun Y, Lee J (2015) Effect of a double-coated probiotic formulation on functional constipation in the elderly: a randomized, double blind, controlled study. Arch Pharm Res 38:1345–1350CrossRefGoogle Scholar
  12. 12.
    Cani PD, Osto M, Geurts L, Everard A (2012) Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 3:279–288CrossRefGoogle Scholar
  13. 13.
    Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, Paek KS, Lee Y, Park JH (2006) Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 1761:736–744CrossRefGoogle Scholar
  14. 14.
    Takemura N, Okubo T, Sonoyama K (2010) Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Exp Biol Med (Maywood) 235:849–856CrossRefGoogle Scholar
  15. 15.
    Yin YN, Yu QF, Fu N, Liu XW, Lu FG (2010) Effects of four Bifidobacteria on obesity in high-fat diet induced rats. World J Gastroenterol 16:3394–3401CrossRefGoogle Scholar
  16. 16.
    Kumar M, Nagpal R, Kumar R, Hemalatha R, Verma V, Kumar A, Chakraborty C, Singh B, Marotta F, Jain S, Yadav H (2012) Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp Diabetes Res 2012:902917CrossRefGoogle Scholar
  17. 17.
    Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez-Humaran LG, Smirnova N, Berge M, Sulpice T, Lahtinen S, Ouwehand A, Langella P, Rautonen N, Sansonetti PJ, Burcelin R (2011) Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med 3:559–572CrossRefGoogle Scholar
  18. 18.
    Stenman LK, Burcelin R, Lahtinen S (2015) Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans—towards treatment with probiotics. Benef Microbes 7:1–12Google Scholar
  19. 19.
    Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023CrossRefGoogle Scholar
  20. 20.
    Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075CrossRefGoogle Scholar
  21. 21.
    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108CrossRefGoogle Scholar
  22. 22.
    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:1470–1481CrossRefGoogle Scholar
  23. 23.
    Jung UJ, Choi MS (2014) Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 15:6184–6223CrossRefGoogle Scholar
  24. 24.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772CrossRefGoogle Scholar
  25. 25.
    Yi LZ, He J, Liang YZ, Yuan DL, Chau FT (2006) Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDA. FEBS Lett 580:6837–6845CrossRefGoogle Scholar
  26. 26.
    Eisinger K, Liebisch G, Schmitz G, Aslanidis C, Krautbauer S, Buechler C (2014) Lipidomic analysis of serum from high fat diet induced obese mice. Int J Mol Sci 15:2991–3002CrossRefGoogle Scholar
  27. 27.
    Abbott MJ, Tang T, Sul HS (2010) The role of phospholipase A(2)-derived mediators in obesity. Drug Discov Today Dis Mech 7:e213–e218CrossRefGoogle Scholar
  28. 28.
    Yaligar J, Gopalan V, Kiat OW, Sugii S, Shui G, Lam BD, Henry CJ, Wenk MR, Tai ES, Velan SS (2014) Evaluation of dietary effects on hepatic lipids in high fat and placebo diet fed rats by in vivo MRS and LC-MS techniques. PLoS ONE 9:e91436CrossRefGoogle Scholar
  29. 29.
    Kim HJ, Kim JH, Noh S, Hur HJ, Sung MJ, Hwang JT, Park JH, Yang HJ, Kim MS, Kwon DY, Yoon SH (2011) Metabolomic analysis of livers and serum from high-fat diet induced obese mice. J Proteome Res 10:722–731CrossRefGoogle Scholar
  30. 30.
    Kim HY, Kim M, Park HM, Kim J, Kim EJ, Lee CH, Park JH (2014) Lysophospholipid profile in serum and liver by high-fat diet and tumor induction in obesity-resistant BALB/c mice. Nutrition 30:1433–1441CrossRefGoogle Scholar
  31. 31.
    Kim JY, Park JY, Kim OY, Ham BM, Kim HJ, Kwon DY, Jang Y, Lee JH (2010) Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). J Proteome Res 9:4368–4375CrossRefGoogle Scholar
  32. 32.
    Vargas-Robles H, Rios A, Arellano-Mendoza M, Escalante BA, Schnoor M (2015) Antioxidative diet supplementation reverses high-fat diet-induced increases of cardiovascular risk factors in mice. Oxid Med Cell Logev 2015:467471Google Scholar
  33. 33.
    Vecka M, Richterova B, Zak A, Tvrzicka E, Sramkova P, Stankova B, Klimcakova E, Stich V (2006) Changes in serum and adipose tissue fatty acid composition after low calorie diet with respect to dietary fat content in obese. Cas Lek Cesk 145:464–469Google Scholar
  34. 34.
    Kotronen A, Velagapudi VR, Yetukuri L, Westerbacka J, Bergholm R, Ekroos K, Makkonen J, Taskinen MR, Oresic M, Yki-Jarvinen H (2009) Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations. Diabetologia 52:684–690CrossRefGoogle Scholar
  35. 35.
    Lee SJ, Bose S, Seo JG, Chung WS, Lim CY, Kim H (2014) The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: a randomized double-blind controlled clinical trial. Clin Nutr 33:973–981CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Joo-Hyun Shin
    • 1
  • Myung Hee Nam
    • 2
  • Hyerim Lee
    • 2
  • Joong-Su Lee
    • 1
  • Hojun Kim
    • 3
  • Myung-Jun Chung
    • 1
  • Jae-Gu Seo
    • 1
  1. 1.R&D Center, Cell Biotech Co., Ltd.Gimpo-siRepublic of Korea
  2. 2.Environmental Risk and Welfare Research TeamKorea Basic Science Institute (KBSI)SeoulRepublic of Korea
  3. 3.Department of Rehabilitation Medicine of Korean MedicineDongguk UniversityGoyang-siRepublic of Korea

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