Skip to main content
SpringerLink
Log in

Diet supplemented with phytochemical epigallocatechin gallate and probiotic Lactobacillus fermentum confers second generation synbiotic effects by modulating cellular immune responses and antioxidant capacity in aging mice

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

A Correction to this article was published on 28 June 2019

This article has been updated

Abstract

Purpose

In the present study, we systematically identified and evaluated a synbiotic combination of phytochemical epigallocatechin gallate (EGCG) and probiotic bacteria in amelioration of immunosenescence and oxidative stress in aged mice.

Methods

Inhibitory effects of EGCG against different bacterial species were evaluated in vitro, followed by analysis to identify potential combination of EGCG and probiotic bacteria against alleviation of oxidative and inflammatory stress ex vivo. The best synbiotic combination, vis-à-vis prebiotic and probiotic supplementation alone, was then evaluated in aged Swiss albino mice for modulation of various immunological and antioxidative parameters.

Results

EGCG strongly inhibited the growth of pathogenic microbes as compared to probiotic bacteria. A combination of EGCG with probiotic Lactobacillus fermentum (LF) provided evidence of additive effects in the amelioration of oxidative and inflammatory stress-induced cell death. In vivo study revealed that combined supplementation of LF and EGCG significantly enhanced neutrophil oxidative index, CD3+ cell numbers and activation status, Th1/Th2 cytokines in splenic supernatants as well as liver Nrf-2 expression in comparison with treatments with LF or EGCG alone. The combined application of EGCG and LF did not simply result in additive or synergistic effects in relation with individual treatments.

Conclusion

These observations suggest that EGCG could be considered as a potential prebiotic that can offer second generation synbiotic health beneficial effects for the alleviation of some of the deleterious aspects of immunosenescence and aging.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Change history

  • 28 June 2019

    Authors of the original article have observed an inadvertent error in their manuscript post-publication.

Abbreviations

EGCG:

Epigallocatechin gallate

LF:

Lactobacillus fermentum

LR:

Lactobacillus rhamnosus

LP:

Lactobacillus planatarum

tBHP:

Tert-Butyl hydroperoxide

PRE:

Prebiotic

PRO:

Probiotic

SYN:

Synbiotic

PBMCs:

Peripheral blood mononuclear cells

PCM:

Probiotic-conditioned media

NF-κB:

Nuclear factor kappa-light-chain enhancer of activated B cells

References

  1. Aw D, Silva AB, Palmer DB (2007) Immunosenescence: emerging challenges for an ageing population. Immunology 120(4):435–446

    Article  CAS  Google Scholar 

  2. Verburgh K (2015) Nutrigerontology: why we need a new scientific discipline to develop diets and guidelines to reduce the risk of aging-related diseases. Aging Cell 14(1):17–24

    Article  CAS  Google Scholar 

  3. Sharma R, Kapila R, Kapila S (2013) Probiotics as anti-immunosenescence agents. Food Rev Int 29(2):201–216

    Article  Google Scholar 

  4. Kerry RG, Patrab JK, Goudac S, Park Y, Shin HS, Das G (2018) Benefaction of probiotics for human health: a review. J Food Drug Anal. https://doi.org/10.1016/j.jfda.2018.01.002

    Article  Google Scholar 

  5. Vodnar DC, Socaciu C (2012) Green tea increases the survival yield of Bifidobacteria in simulated gastrointestinal environment and during refrigerated conditions. Chem Cent J 6(1):61

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ampatzoglou A, Atwal KK, Maidens CM, Williams CL, Ross AB, Thielecke F, Jonnalagadda SS, Kennedy OB, Yaqoob P (2015) Increased whole grain consumption does not affect blood biochemistry, body composition, or gut microbiology in healthy, low-habitual whole grain consumers. J Nutr 145(2):215–221

    Article  Google Scholar 

  7. Hollænder PL, Ross AB, Kristensen M (2015) Whole-grain and blood lipid changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies. Am J Clin Nutr 102(3):556–572

    Article  Google Scholar 

  8. Bindels LB, Delzenne NM, Cani PD, Walter J (2015) Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol 12(5):303–310

    Article  CAS  Google Scholar 

  9. Krumbeck JA, Maldonado-Gomez MX, Ramer-Tait AE, Hutkins RW (2016) Prebiotics and synbiotics: dietary strategies for improving gut health. Curr Opin Gastroenterol 32(2):110–119

    Article  CAS  Google Scholar 

  10. Lee HC, Jenner AM, Low CS, Lee YK (2006) Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res Microbiol 157(9):876–884

    Article  CAS  Google Scholar 

  11. Su P, Henriksson A, Nilsson C, Mitchell H (2008) Synergistic effect of green tea extract and probiotics on the pathogenic bacteria, Staphylococcus aureus and Streptococcus pyogenes. World J Microbiol Biotechnol 24:1837–1842

    Article  Google Scholar 

  12. Sourabh A, Kanwar SS, Sud RG, Ghabru A, Sharma OP (2014) Influence of phenolic compounds of Kangra tea [Camellia sinensis (L) O Kuntze] on bacterial pathogens and indigenous bacterial probiotics of Western Himalayas. Braz J Microbiol 44(3):709–715

    Article  Google Scholar 

  13. Banerjee A, Dhar P (2018) Amalgamation of polyphenols and probiotics induce health promotion. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2018.1478795

    Article  PubMed  Google Scholar 

  14. Kumari M, Swarnkar MK, Kumar S, Singh AK, Gupta M (2015) Genome sequence of a potential probiotic strain, Lactobacillus fermentum HFB3, isolated from a human Gut. Genome Announc 3(6):e01296–e01315

    Google Scholar 

  15. Kumari M, Swarnkar MK, Kumar S, Singh AK, Gupta M (2015) Complete genome sequence of potential probiotic Lactobacillus sp. HFC8, isolated from human gut using PacBio SMRT sequencing. Genome Announc 3(6):e01315–e01337

    Google Scholar 

  16. Sharma R, Sharma A, Kumari A, Kulurkar PM, Raj R, Gulati A, Padwad YS (2017) Consumption of green tea epigallocatechin-3-gallate enhances systemic immune response, antioxidative capacity and HPA axis functions in aged male swiss albino mice. Biogerontology 18(3):367–382

    Article  CAS  Google Scholar 

  17. Crowley LC, Scott AP, Marfell BJ, Boughaba JA, Chojnowski G, Waterhouse NJ (2016) Measuring cell death by propidium iodide uptake and flow cytometry. Cold Spring Harb Protoc 7:pdb.prot087163

    Article  Google Scholar 

  18. Sharma R, Kapila R, Haq MR, Salingati V, Kapasiya M, Kapila S (2014) Age-associated aberrations in mouse cellular and humoral immune responses. Aging Clin Exp Res 26(4):353–362

    Article  Google Scholar 

  19. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239–252

    Article  CAS  Google Scholar 

  20. Mair KH, Stadler M, Talker SC, Forberg H, Storset AK, Müllebner A, Duvigneau JC, Hammer SE, Saalmuller A, Gerner W (2016) Porcine CD3+NKp46+ lymphocytes have NK-cell characteristics and are present in increased frequencies in the lungs of influenza-infected animals. Front Immun 7:263

    Article  Google Scholar 

  21. Pirson C, Engel R, Jones GJ, Holder T, Holst O, Vordermeier HM (2015) Highly purified mycobacterial phosphatidylinositol mannosides drive cell-mediated responses and activate NKT cells in cattle. Clin Vaccine Immunol 22(2):178–184

    Article  Google Scholar 

  22. You J, Yaqoob P (2012) Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486. FEMS Immunol Med Microbiol 66(3):353–362

    Article  CAS  Google Scholar 

  23. Mahnke YD, Roederer M (2007) Optimizing a multicolor immunophenotyping assay. Clin Lab Med 27(3):469–485

    Article  Google Scholar 

  24. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  25. Zhang X, Zhu X, Sun Y, Hu B, Sun Y, Jabbar S, Zeng X (2013) Fermentation in vitro of EGCG, GCG and EGCG3"Me isolated from Oolong tea by human intestinal microbiota. Food Res Int 54(2):1589–1595

    Article  CAS  Google Scholar 

  26. Sharma R, Kapila R, Dass G, Kapila S (2014) Improvement in Th1/Th2 immune homeostasis, antioxidative status and resistance to pathogenic E. coli on consumption of probiotic Lactobacillus rhamnosus fermented milk in aging mice. Age (Dordr) 36(4):9686

    Article  Google Scholar 

  27. Unno K (2016) Prevention of brain aging by green tea components: role of catechins and theanine. J Sports Med Phys Fit 5(2):117–122

    Article  Google Scholar 

  28. Landete JM, Gaya P, Rodríguez E, Langa S, Peirotén Á, Medina M, Arqués JL (2017) Probiotic bacteria for healthier aging: immunomodulation and metabolism of phytoestrogens. Biomed Res Int. https://doi.org/10.1155/2017/5939818

    Article  PubMed  PubMed Central  Google Scholar 

  29. Arena MP, Russo P, Capozzi V, Rascon A, Felis GE, Spano G, Fiocco D (2016) Combinations of cereal β-glucans and probiotics can enhance the anti-inflammatory activity on host cells by a synergistic effect. J Funct Foods 23:12–23

    Article  CAS  Google Scholar 

  30. Roller M, Pietro Femia A, Caderni G, Rechkemmer G, Watzl B (2004) Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis. Br J Nutr 92(6):931–938

    Article  CAS  Google Scholar 

  31. Nikolich-Žugich J (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193(6):2622–2629. https://doi.org/10.4049/jimmunol.1401174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jagger A, Shimojima Y, Goronzy JJ, Weyand CM (2014) Regulatory T cells and the immune aging process: a mini-review. Gerontology 60(2):130–137

    Article  CAS  Google Scholar 

  33. Smelt MJ, de Haan BJ, Bron PA, van Swam I, Meijerink M, Wells JM, Faas MM, de Vos P (2013) Probiotics can generate FoxP3 T-cell responses in the small intestine and simultaneously inducing CD4 and CD8 T cell activation in the large intestine. PLoS One 4(7):e68952 8(

    Article  Google Scholar 

  34. Lutz CT, Moore MB, Bradley S, Shelton BJ, Lutgendorf SK (2005) Reciprocal age related change in natural killer cell receptors for MHC class I. Mech Ageing Dev 126:722–731

    Article  CAS  Google Scholar 

  35. Le Garff-Tavernier M, Béziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debré P, Merle-Beral H, Vieillard V (2010) Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9(4):527–535. https://doi.org/10.1111/j.1474-9726.2010.00584.x

    Article  CAS  PubMed  Google Scholar 

  36. Lutz CT, Karapetyan A, Al-Attar A, Shelton BJ, Holt KJ, Tucker JH, Presnell SR (2011) Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults. J immunol 186:4590–4598

    Article  CAS  Google Scholar 

  37. Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11:751–759

    Article  CAS  Google Scholar 

  38. Zhang Y, Wallace DL, de Lara CM, Ghattas H, Asquith B, Worth A, Griffin GE, Taylor GP, Tough DF, Beverley PC, Macallan DC (2007) In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunol 121:258–265

    Article  CAS  Google Scholar 

  39. Solana R, Alonso MC, Peña J (1999) Natural killer cells in healthy aging. Exp Gerontol 34(3):435–443

    Article  CAS  Google Scholar 

  40. Tymoshok NO, Lazarenko LM, Bubnov RV, Shynkarenko LN, Babenko LP, Mokrozub VV, Melnichenko YA, Spivak MY (2014) New aspects the regulation of immune response through balance Th1/Th2 cytokines. EPMA Journal 5(Suppl 1):A134

    Article  Google Scholar 

  41. Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD (2011) NF-κB in aging and disease. Aging Dis 2(6):449–465

    PubMed  PubMed Central  Google Scholar 

  42. Zhang H, Davies KJA, Forman HJ (2015) Oxidative stress response and Nrf2 signaling in aging. Free Radic Biol Med 88(Pt B):314–336

    Article  CAS  Google Scholar 

  43. Xu J, Jönsson T, Plaza M, Håkansson Å, Antonsson M, Ahrén IL, Turner C, Spégel P, Granfeldt Y (2018) Probiotic fruit beverages with different polyphenol profiles attenuated early insulin response. Nutr J 17(1):34

    Article  Google Scholar 

  44. Krautkramer KA, Rey FE, Denu JM (2017) Chemical signaling betweengut microbiota and host chromatin: what is your gut really saying? J Biol Chem 292(21):8582–8593

    Article  CAS  Google Scholar 

  45. Wang Y, Liu Y, Sidhu A, Ma Z, McClain C, Feng W (2012) Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury. Am J Physiol Gastrointest Liver Physiol 303(1):G32–G41

    Article  CAS  Google Scholar 

  46. Seenappanahalli Nanjundaiah Y, Wright DA, Baydoun AR, O’Hare WT, Ali Z, Khaled Z, Sarker MH (2016) Lactobacillus rhamnosus GG conditioned media modulates acute reactive oxygen species and nitric oxide in J774 murine macrophages. Biochem Biophys Rep 7:6:68–75

    Google Scholar 

Download references

Acknowledgements

Authors acknowledge the Director, CSIR-IHBT, Palampur for supporting and providing all the necessary facilities. This work was supported by grants from the Science and Engineering Research Board, Government of India, through the Young Scientist Scheme (YSS/2015/000758) and MLP0204 of CSIR Government of India.

Author information

Authors and Affiliations

  1. Pharmacology and Toxicology Laboratory, Food and Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India

    Rohit Sharma, Anamika Sharma & Yogendra Padwad

  2. Food and Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India

    Madhu Kumari, Amita Kumari, Ashu Gulati & Mahesh Gupta

Authors
  1. Rohit Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhu Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amita Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anamika Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ashu Gulati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mahesh Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yogendra Padwad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Rohit Sharma or Yogendra Padwad.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 857 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, R., Kumari, M., Kumari, A. et al. Diet supplemented with phytochemical epigallocatechin gallate and probiotic Lactobacillus fermentum confers second generation synbiotic effects by modulating cellular immune responses and antioxidant capacity in aging mice. Eur J Nutr 58, 2943–2957 (2019). https://doi.org/10.1007/s00394-018-01890-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-018-01890-6

Keywords

Search

Navigation