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
Yuan Q, Walker WA (2004) Innate immunity of the gut: Mucosal defense in health and disease. J Pediatr Gastroenterol Nutr 38(5):463–473
Lazarev VN, Govorun VM (2010) Antimicrobial peptides and their use in medicine. Appl Biochem Microbiol 46(9):803–814
Muller CA, Autenrieth IB, Peschel A (2005) Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 62(12):1297–1307
Ganz T (2003) Defensins: Antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Ding QM, Wang QD, Evers BM (2001) Alterations of MAPK activities associated with intestinal cell differentiation. Biochem Biophys Res Commun 284(2):282–288
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
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
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
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
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
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
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
Acknowledgments
This work was funded by ZESPRI International Limited, New Zealand. We thank Halina Stoklosinski and Doug Rosendale for SCFA analyses.
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The authors declare that they have no conflict of interest.
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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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DOI: https://doi.org/10.1007/s11130-012-0305-1