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Digested and Fermented Green Kiwifruit Increases Human β-Defensin 1 and 2 Production In vitro

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Abstract

The intestinal mucosa is constantly exposed to a variety of microbial species including commensals and pathogens, the latter leaving the host susceptible to infection. Antimicrobial peptides (AMP) are an important part of the first line of defense at mucosal surfaces. Human β-defensins (HBD) are AMP expressed by colonic epithelial cells, which act as broad spectrum antimicrobials. This study explored the direct and indirect effects of green kiwifruit (KF) on human β-defensin 1 and 2 (HBD-1 and 2) production by epithelial cells. In vitro digestion of KF pulp consisted of a simulated gastric and duodenal digestion, followed by colonic microbial fermentation using nine human faecal donors. Fermenta from individual donors was sterile filtered and independently added to epithelial cells prior to analysis of HBD protein production. KF products obtained from the gastric and duodenal digestion had no effect on the production of HBD-1 or 2 by epithelial cells, demonstrating that KF does not contain substances that directly modulate defensin production. However, when the digested KF products were further subjected to in vitro colonic fermentation, the fermentation products significantly up-regulated HBD-1 and 2 production by the same epithelial cells. We propose that this effect was predominantly mediated by the presence of short-chain fatty acids (SCFA) in the fermenta. Exposure of cells to purified SCFA confirmed this and HBD-1 and 2 production was up-regulated with acetate, propionate and butyrate. In conclusion, in vitro colonic fermentation of green kiwifruit digest appears to prime defense mechanisms in gut cells by enhancing the production of antimicrobial defensins.

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Abbreviations

AMP:

Antimicrobial peptides

GD:

Green kiwifruit digesta

CD:

Control digesta

E. coli LF82:

Escherichia coli LF82

E. coli Nissle:

Escherichia coli Nissle

GF:

Fermented green kiwifruit digesta

CF:

Fermented control digesta

KF:

Green kiwifruit

HBD:

Human β-defensins

LPS:

Lipopolysaccharides

L. monocytogenes Scott A:

Listeria monocytogenes Scott A

PGN:

Peptidoglycan

SCFA:

Short chain fatty acids

S. typhimurium :

Salmonella enterica serovar Typhimurium

S. aureus :

Staphylococcus aureus

TLR:

Toll-like receptor

References

  1. Yuan Q, Walker WA (2004) Innate immunity of the gut: Mucosal defense in health and disease. J Pediatr Gastroenterol Nutr 38(5):463–473

    Article  CAS  Google Scholar 

  2. Lazarev VN, Govorun VM (2010) Antimicrobial peptides and their use in medicine. Appl Biochem Microbiol 46(9):803–814

    Article  CAS  Google Scholar 

  3. Muller CA, Autenrieth IB, Peschel A (2005) Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 62(12):1297–1307

    Article  CAS  Google Scholar 

  4. Ganz T (2003) Defensins: Antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720

    Article  CAS  Google Scholar 

  5. Sherman H, Froy O (2008) Expression of human beta-defensin 1 is regulated via c-Myc and the biological clock. Mol Immunol 45(11):3163–3167

    Article  CAS  Google Scholar 

  6. Wang H, Mannava S, Grachtchouk V, Zhuang D, Soengas MS, Gudvok AV, Prochownik EV, Nikiforov MA (2008) c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle. Oncogene 27(13):1905–1915

    Article  CAS  Google Scholar 

  7. Blottiere HM, Buecher B, Galmiche JP, Cherbut C (2003) Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation. Proc Nutr Soc 62(1):101–106

    Article  CAS  Google Scholar 

  8. O’Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, Kagnoff MF (1999) Expression and regulation of the human beta-defensins HBD-1 and HBD-2 in intestinal epithelium. J Immunol 163(12):6718–6724

    Google Scholar 

  9. Wehkamp J, Harder J, Wehkamp K, Wehkamp-von Meissner B, Schlee M, Enders C, Sonnenborn U, Nuding S, Bengmark S, Fellermann K, Schröder JM, Stange EF (2004) NF-kappa B- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: A novel effect of a probiotic bacterium. Infect Immun 72(10):5750–5758

    Article  CAS  Google Scholar 

  10. Yoon YM, Lee JY, Yoo D, Sim YS, Kim YJ, Oh YK, Kang JS, Kim S, Kim JS, Kim JM (2010) Bacteroides fragilis enterotoxin induces human beta-defensin-2 expression in intestinal epithelial cells via a mitogen-activated protein kinase/I kappa B kinase/NF-kappa B-dependent pathway. Infect Immun 78(5):2024–2033

    Article  CAS  Google Scholar 

  11. Paolillo R, Carratelli CR, Sorrentino S et al (2009) Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells. Int Immunopharmacol 9(11):1265–1271

    Article  CAS  Google Scholar 

  12. Paolillo R, Romano Carratelli C, Sorrentino S, Mazzola N, Rizzo A (2008) The dietary histone deacetylase inhibitor sulforaphane induces human beta-defensin-2 in intestinal epithelial cells. Immunology 125(2):241–251

    Article  CAS  Google Scholar 

  13. Schauber J, Dorschner RA, Yamasaki K, Brouha B, Gallo RL (2006) Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmentat stimuli. Immunology 118(4):509–519

    CAS  Google Scholar 

  14. Parkar SG, Rosendale D, Paturi G, Herath TD, Stoklosinski H, Phipps JE, Hedderley D, Ansell J (2012) In vitro utilization of gold and green kiwifruit oligosaccharides by human gut microbial populations. Plant Foods Hum Nutr. doi:10.1007/s11130-012-0293-1

  15. Lu Y, Zhao YP, Fu CX (2011) Biological activities of extracts from a naturally wild kiwifruit, Actinidia macrosperma. Afr J Agric Res 6(10):2231–2234

    Google Scholar 

  16. Monro JA, Mishra S, Venn B (2010) Baselines representing blood glucose clearance improve in vitro prediction of the glycaemic impact of customarily consumed food quantities. Br J Nutr 103(2):295–305

    Article  CAS  Google Scholar 

  17. Richardson AJ, Calder AG, Stewart CS, Smith A (1989) Simultaneous determination of volatile and non-volatile acidic fermentation products of anaerobes by capillary gas-chromatography. Lett Appl Microbiol 9(1):5–8

    Article  CAS  Google Scholar 

  18. Paturi G, Butts C, Monro J, Nones K, Martell S, Butler R, Sutherland J (2010) Cecal and colonic responses in rats fed 5 or 30 % corn oil diets containing either 7.5 % broccoli dietary fiber or microcrystalline cellulose. J Agric Food Chem 58(10):6510–6515

    Article  CAS  Google Scholar 

  19. Furrie E, Macfarlane S, Thomson G, Macfarlane GT (2005) Toll-like receptors-2, -3 and -4 expression patterns on human colon and their regulation by mucosal-associated bacteria. Immunology 115(4):565–574

    Article  CAS  Google Scholar 

  20. Wiegand I, Hilpert K, Hancock REW (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3(2):163–175

    Article  CAS  Google Scholar 

  21. Ding QM, Wang QD, Evers BM (2001) Alterations of MAPK activities associated with intestinal cell differentiation. Biochem Biophys Res Commun 284(2):282–288

    Article  CAS  Google Scholar 

  22. Yang JQ, Kawai Y, Hanson RW, Arinze IJ (2001) Sodium butyrate induces transcription from the G alpha(i2) gene promoter through multiple Sp1 sites in the promoter and by activating the MEK-ERK signal transduction pathway. J Biol Chem 276(28):25742–25752

    Article  CAS  Google Scholar 

  23. Schwab M, Reynders V, Shastri Y, Loitsch S, Stein J, Schröder O (2007) Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells. Mol Immunol 44(8):2107–2114

    Article  Google Scholar 

  24. Schauber J, Iffland K, Frisch S, Kudlich T, Schmausser B, Eck M, Menzel T, Gostner A, Lührs H, Scheppach W (2004) Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells. Mol Immunol 41(9):847–854

    Article  CAS  Google Scholar 

  25. McBain JA, Eastman A, Nobel CS, Mueller GC (1997) Apoptotic death in adenocarcinoma cell lines induced by butyrate and other histone deacetylase inhibitors. Biochem Pharmacol 53(9):1357–1368

    Article  CAS  Google Scholar 

  26. Kuwano K, Tanaka N, Shimizu T, Kida Y (2006) Antimicrobial activity of inducible human beta defensin-2 against Mycoplasma pneumoniae. Curr Microbiol 52(6):435–438

    Article  CAS  Google Scholar 

  27. Schroeder BO, Wu Z, Nuding S et al (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469(7330):419–423

    Article  CAS  Google Scholar 

  28. Joeres-Nguyen-Xuan TH, Boehm SK, Joeres L, Schulze J, Kruis W (2010) Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers. Inflamm Bowel Dis 16(2):256–262

    Google Scholar 

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Acknowledgments

This work was funded by ZESPRI International Limited, New Zealand. We thank Halina Stoklosinski and Doug Rosendale for SCFA analyses.

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Correspondence to Kerry L. Bentley-Hewitt.

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Bentley-Hewitt, K.L., Blatchford, P.A., Parkar, S.G. et al. Digested and Fermented Green Kiwifruit Increases Human β-Defensin 1 and 2 Production In vitro . Plant Foods Hum Nutr 67, 208–214 (2012). https://doi.org/10.1007/s11130-012-0305-1

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