European Journal of Nutrition

, Volume 56, Issue 2, pp 649–661 | Cite as

Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults

  • Huicui Meng
  • Zhaoyong Ba
  • Yujin Lee
  • Jiayu Peng
  • Junli Lin
  • Jennifer A. Fleming
  • Emily J. Furumoto
  • Robert F. Roberts
  • Penny M. Kris-Etherton
  • Connie J. Rogers
Original Contribution

Abstract

Purpose

Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix.

Methods

Healthy adults (n = 30) aged 18–40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed.

Results

BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14+HLA-DR+ cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14+HLA-DR+ cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline.

Conclusions

These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

Keywords

Probiotics BB-12 Delivery matrix Inflammation TNF-α 

Abbreviations

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor alpha

IL-6

Interleukin 6

GI

Gastrointestinal

MoDCs

Monocyte-derived dendritic cells

COX-2

Cyclooxygenase-2

IBD

Inflammatory bowel disease

IBS

Irritable bowel syndrome

CFU

Colony-forming unit

MRS

de Man, Rogosa, and Sharpe

NNLP

Nalidixic acid, neomycin sulfate, lithium chloride, and paromomycin sulfate

DCs

Dendritic cells

LPS

Lipopolysaccharide

PBMC

Peripheral blood mononuclear cell

CRC

Clinical Research Center

BMI

Body mass index

PA

Physical activity

IPAQ

International Physical Activity Questionnaire

hs-CRP

High-sensitivity C-reactive protein

MFI

Mean fluorescence intensity

n-3 PUFA

n-3 Polyunsaturated fatty acids

MET

Metabolic equivalent of task

BL

Baseline

YS

Yogurt smoothie

PRE

Pre-fermentation

POST

Post-fermentation

CAP

Capsule

IEC

Intestinal epithelial cell

NF-κB

Nuclear factor-κB

SOCS

Suppressor of cytokine signaling

Notes

Acknowledgments

J.A.F., P.K.E., R.F.R., and C.J.R. designed the research; H.M., Z.B., Y.L., and E.J.F. conducted the research; J.P., J.L., and H.M. analyzed the data; H.M. and C.J.R. wrote the paper; and C.J.R. had primary responsibility for the final content. All authors read and approved the final manuscript. This research was supported by a grant from the Dairy Research Institute and the Broadhurst Career Development Fund. Graduate Research Fellowships were provided through the Departments of Food Science and Nutritional Sciences at the Pennsylvania State University.

Compliance with ethical standards

Conflict of interest

H. Meng, Z. Ba, Y. Lee, J. Peng, J. Lin, J.A. Fleming, E.J. Furumoto, R.F. Roberts, P.M. Kris-Etherton, and C.J. Rogers have no conflicts of interest.

Supplementary material

394_2015_1109_MOESM1_ESM.pdf (61 kb)
Supplementary material 1 (PDF 61 kb)
394_2015_1109_MOESM2_ESM.pdf (111 kb)
Supplementary material 2 (PDF 111 kb)
394_2015_1109_MOESM3_ESM.pdf (67 kb)
Supplementary material 3 (PDF 67 kb)

References

  1. 1.
    Lomax AR, Calder PC (2009) Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr Pharm Des 15(13):1428–1518CrossRefGoogle Scholar
  2. 2.
    Jungersen M, Wind A, Johansen E, Christensen J, Stuer-Lauridsen B, Eskesen D (2014) The science behind the probiotic strain Bifidobacterium animalis subsp. lactis BB-12®. Microorganisms 2(2):92–110. doi: 10.3390/microorganisms2020092 CrossRefGoogle Scholar
  3. 3.
    Vernazza CL, Gibson GR, Rastall RA (2006) Carbohydrate preference, acid tolerance and bile tolerance in five strains of Bifidobacterium. J Appl Microbiol 100(4):846–853. doi: 10.1111/j.1365-2672.2006.02832.x CrossRefGoogle Scholar
  4. 4.
    Vinderola CG, Reinheimer JA (2003) Lactic acid starter and probiotic bacteria: a comparative “in vitro” study of probiotic characteristics and biological barrier resistance. Food Res Int 36(9–10):895–904. doi: 10.1016/s0963-9969(03)00098-x CrossRefGoogle Scholar
  5. 5.
    He F, Ouwehan AC, Hashimoto H, Isolauri E, Benno Y, Salminen S (2001) Adhesion of Bifidobacterium spp. to human intestinal mucus. Microbiol Immunol 45(3):259–262CrossRefGoogle Scholar
  6. 6.
    Laparra JM, Sanz Y (2009) Comparison of in vitro models to study bacterial adhesion to the intestinal epithelium. Lett Appl Microbiol 49(6):695–701. doi: 10.1111/j.1472-765X.2009.02729.x CrossRefGoogle Scholar
  7. 7.
    Christensen HR, Larsen CN, Kaestel P, Rosholm LB, Sternberg C, Michaelsen KF, Frokiaer H (2006) Immunomodulating potential of supplementation with probiotics: a dose-response study in healthy young adults. FEMS Immunol Med Microbiol 47(3):380–390. doi: 10.1111/j.1574-695X.2006.00109.x CrossRefGoogle Scholar
  8. 8.
    Rizzardini G, Eskesen D, Calder PC, Capetti A, Jespersen L, Clerici M (2012) Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12(R) and Lactobacillus paracasei ssp. paracasei, L. casei 431(R) in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr 107(6):876–884. doi: 10.1017/S000711451100420X CrossRefGoogle Scholar
  9. 9.
    Schiffrin EJ, Rochat F, Link-Amster H, Aeschlimann JM, Donnet-Hughes A (1995) Immunomodulation of human blood cells following the ingestion of lactic acid bacteria. J Dairy Sci 78(3):491–497. doi: 10.3168/jds.S0022-0302(95)76659-0 CrossRefGoogle Scholar
  10. 10.
    Lopez P, Gueimonde M, Margolles A, Suarez A (2010) Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol 138(1–2):157–165. doi: 10.1016/j.ijfoodmicro.2009.12.023 CrossRefGoogle Scholar
  11. 11.
    Kajander K, Myllyluoma E, Rajilic-Stojanovic M, Kyronpalo S, Rasmussen M, Jarvenpaa S, Zoetendal EG, de Vos WM, Vapaatalo H, Korpela R (2008) Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther 27(1):48–57. doi: 10.1111/j.1365-2036.2007.03542.x CrossRefGoogle Scholar
  12. 12.
    Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C (2005) Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 147(2):192–196. doi: 10.1016/j.jpeds.2005.03.054 CrossRefGoogle Scholar
  13. 13.
    Philippe D, Favre L, Foata F, Adolfsson O, Perruisseau-Carrier G, Vidal K, Reuteler G, Dayer-Schneider J, Mueller C, Blum S (2011) Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis. World J Gastroenterol 17(4):459–469. doi: 10.3748/wjg.v17.i4.459 CrossRefGoogle Scholar
  14. 14.
    Nanau RM, Neuman MG (2012) Nutritional and probiotic supplementation in colitis models. Dig Dis Sci 57(11):2786–2810. doi: 10.1007/s10620-012-2284-3 CrossRefGoogle Scholar
  15. 15.
    Kekkonen RA, Lummela N, Karjalainen H, Latvala S, Tynkkynen S, Jarvenpaa S, Kautiainen H, Julkunen I, Vapaatalo H, Korpela R (2008) Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults. World J Gastroenterol 14(13):2029–2036CrossRefGoogle Scholar
  16. 16.
    Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T (1991) A human Lactobacillus strain (Lactobacillus casei sp. strain GG) promotes recovery from acute diarrhea in children. Pediatrics 88(1):90–97Google Scholar
  17. 17.
    Sanders ME, Marco ML (2010) Food formats for effective delivery of probiotics. Annu Rev Food Sci Technol 1:65–85. doi: 10.1146/annurev.food.080708.100743 CrossRefGoogle Scholar
  18. 18.
    Granato D, Branco GF, Nazzaro F, Cruz AG, Faria JA (2010) Functional foods and nondairy probiotic food development: trends, concepts, and products. Comp Rev Food Sci Food Saf 9(3):292–302CrossRefGoogle Scholar
  19. 19.
    Merenstein D, Gonzalez J, Young AG, Roberts RF, Sanders ME, Petterson S (2011) Study to investigate the potential of probiotics in children attending school. Eur J Clin Nutr 65(4):447–453. doi: 10.1038/ejcn.2010.290 CrossRefGoogle Scholar
  20. 20.
    Laroia S, Martin JH (1991) Methods for enumerating and propagating bifidobacteria. Cult Dairy Prod J 26(2):32–34Google Scholar
  21. 21.
    Bouchard C, Tremblay A, Leblanc C, Lortie G, Savard R, Theriault G (1983) A method to assess energy expenditure in children and adults. Am J Clin Nutr 37(3):461–467Google Scholar
  22. 22.
    Meng H, Lee Y, Ba Z, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ (2015) In vitro production of IL-6 and IFN-γ is influenced by dietary variables and predicts upper respiratory tract infection incidence and severity respectively in young adults. Front Immunol 6 (94). doi: 10.3389/fimmu.2015.00094
  23. 23.
    Ruiz PA, Hoffmann M, Szcesny S, Blaut M, Haller D (2005) Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germ-free rats. Immunology 115(4):441–450. doi: 10.1111/j.1365-2567.2005.02176.x CrossRefGoogle Scholar
  24. 24.
    Shahani KM, Chandan RC (1979) Nutritional and healthful aspects of cultured and culture-containing dairy foods. J Dairy Sci 62(10):1685–1694. doi: 10.3168/jds.S0022-0302(79)83481-5 CrossRefGoogle Scholar
  25. 25.
    Sachdeva A, Nagpal J (2009) Effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication: a systematic review and meta-analysis of randomized-controlled trials. Eur J Gastroenterol Hepatol 21(1):45–53. doi: 10.1097/MEG.0b013e32830d0eff CrossRefGoogle Scholar
  26. 26.
    Urbanska AM, Bhathena J, Martoni C, Prakash S (2009) Estimation of the potential antitumor activity of microencapsulated Lactobacillus acidophilus yogurt formulation in the attenuation of tumorigenesis in Apc(Min/+) mice. Dig Dis Sci 54(2):264–273. doi: 10.1007/s10620-008-0363-2 CrossRefGoogle Scholar
  27. 27.
    Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135–145. doi: 10.1038/35100529 CrossRefGoogle Scholar
  28. 28.
    Staege H, Schaffner A, Schneemann M (2000) Human toll-like receptors 2 and 4 are targets for deactivation of mononuclear phagocytes by interleukin-4. Immunol Lett 71(1):1–3CrossRefGoogle Scholar
  29. 29.
    Flo TH, Halaas O, Torp S, Ryan L, Lien E, Dybdahl B, Sundan A, Espevik T (2001) Differential expression of Toll-like receptor 2 in human cells. J Leukoc Biol 69(3):474–481Google Scholar
  30. 30.
    Tien MT, Girardin SE, Regnault B, Le Bourhis L, Dillies MA, Coppee JY, Bourdet-Sicard R, Sansonetti PJ, Pedron T (2006) Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J Immunol 176(2):1228–1237CrossRefGoogle Scholar
  31. 31.
    Nakamura YK, Omaye ST (2012) Metabolic diseases and pro- and prebiotics: mechanistic insights. Nutr Metab (Lond) 9(1):60. doi: 10.1186/1743-7075-9-60 CrossRefGoogle Scholar
  32. 32.
    Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR, Vieira LQ, Souza DG, Teixeira MM (2008) Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci USA 105(6):2193–2197. doi: 10.1073/pnas.0711891105 CrossRefGoogle Scholar
  33. 33.
    Okada Y, Tsuzuki Y, Hokari R, Komoto S, Kurihara C, Kawaguchi A, Nagao S, Miura S (2009) Anti-inflammatory effects of the genus Bifidobacterium on macrophages by modification of phospho-I kappaB and SOCS gene expression. Int J Exp Pathol 90(2):131–140. doi: 10.1111/j.1365-2613.2008.00632.x CrossRefGoogle Scholar
  34. 34.
    Riedel CU, Foata F, Philippe D, Adolfsson O, Eikmanns BJ, Blum S (2006) Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-kappaB activation. World J Gastroenterol 12(23):3729–3735CrossRefGoogle Scholar
  35. 35.
    Hepburn NJ, Garaiova I, Williams EA, Michael DR, Plummer S (2013) Probiotic supplement consumption alters cytokine production from peripheral blood mononuclear cells: a preliminary study using healthy individuals. Benef Microbes 4(4):313–317. doi: 10.3920/BM2013.0012 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Huicui Meng
    • 1
  • Zhaoyong Ba
    • 2
  • Yujin Lee
    • 1
  • Jiayu Peng
    • 3
  • Junli Lin
    • 3
  • Jennifer A. Fleming
    • 1
  • Emily J. Furumoto
    • 2
  • Robert F. Roberts
    • 2
  • Penny M. Kris-Etherton
    • 1
  • Connie J. Rogers
    • 1
  1. 1.224 Chandlee Laboratory, Department of Nutritional SciencesPennsylvania State UniversityUniversity ParkUSA
  2. 2.Department of Food SciencePennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of StatisticsPennsylvania State UniversityUniversity ParkUSA

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