Skip to main content
SpringerLink
Log in

Antimicrobial Peptides in the Gut

  • Chapter
  • First Online:
Antimicrobial Peptides

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

The gut represents a unique interface toward our environment. It not only facilitates digestion and resorption but also battles ingested pathogens, while also controlling an immense community of commensal microorganisms. To aid with the latter, it produces a wide range of innate immune mediators, such as antimicrobial peptides (AMPs), which can combat viruses, bacteria, and fungi. Gut AMPs have differing activity ranges and modes of action, so their expression varies depending on the present conditions and threats. The most famous examples for site-specific AMPs are probably the two α-defensins HD5 and HD6. In a homeostatic state, they are exclusive to the Paneth cells of the small intestine. Since the importance of gut microbiota has become more and more evident, research on AMPs has also increased. This is particularly obvious in the case of inflammatory bowel diseases, but also noticeable in other disorders. Defects in the AMP machinery have been linked to increased susceptibility to infections, chronic inflammation, and disturbances in commensal composition. Recently, even a role in colon cancer has been proposed. The gut provides a complex and challenging environment for the study of interactions between AMPs and microbes; and while we are now widely aware of their crucial role in keeping us healthy, more research is needed to fully uncover the involved multi-level crosstalk of their actions. Such investigations might one day help us in fully understanding the mechanisms of various diseases. Even more, they might aid in developing new anti-infectious, antiinflammatory, and maybe even antitumorigenic drugs.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abreu MT (2010) Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol 10:131–144

    Article  CAS  PubMed  Google Scholar 

  • Abreu MT, Fukata M, Arditi M (2005) TLR signaling in the gut in health and disease. J Immunol 174:4453–4460

    Article  CAS  PubMed  Google Scholar 

  • Aldhous MC, Noble CL, Satsangi J (2009) Dysregulation of human beta-defensin-2 protein in inflammatory bowel disease. PLoS One 4:e6285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Amendola A, Butera A, Sanchez M, Strober W, Boirivant M (2014) Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms. Mucosal Immunol 7:391–404

    Article  CAS  PubMed  Google Scholar 

  • Ananthakrishnan AN (2015) Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 12(4):205–217

    Article  PubMed  Google Scholar 

  • Andreu P, Peignon G, Slomianny C, Taketo MM, Colnot S, Robine S, Lamarque D, Laurent-Puig P, Perret C, Romagnolo B (2008) A genetic study of the role of the Wnt/beta-catenin signalling in Paneth cell differentiation. Dev Biol 324:288–296

    Article  CAS  PubMed  Google Scholar 

  • Antoni L, Nuding S, Wehkamp J, Stange EF (2014) Intestinal barrier in inflammatory bowel disease. World J Gastroenterol 20:1165–1179

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Antoni L, Nuding S, Weller D, Gersemann M, Ott G, Wehkamp J, Stange EF (2013) Human colonic mucus is a reservoir for antimicrobial peptides. J Crohns Colitis 7:e652–e664

    Article  PubMed  Google Scholar 

  • Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ (2000) Secretion of microbicidal alpha-defensins by intestinal Paneth cell response to bacteria. Nat Immunol 1(2):113–118

    Article  CAS  PubMed  Google Scholar 

  • Bauer B, Wex T, Kuester D, Meyer T, Malfertheiner P (2013) Differential expression of human beta defensin 2 and 3 in gastric mucosa of Helicobacter pylori-infected individuals. Helicobacter 18:6–12

    Article  CAS  PubMed  Google Scholar 

  • Beisner J, Teltschik Z, Ostaff MJ, Tiemessen MM, Staal FJ, Wang G, Gersemann M, Perminow G, Vatn MH, Schwab M, Stange EF, Wehkamp J (2014) TCF-1 mediated Wnt Signaling regulates Paneth cell innate immune defense effectors HD-5 and −6: implications for Crohn’s disease. Am J Physiol Gastrointest Liver Physiol 307(5):G487–G498

    Article  CAS  PubMed  Google Scholar 

  • Bentley RW, Pearson J, Gearry RB, Barclay ML, McKinney C, Merriman TR, Roberts RL (2009) Association of higher DEFB4 genomic copy number with Crohn’s disease. Am J Gastroenterol 105(2):354–359

    Article  PubMed  CAS  Google Scholar 

  • Bevins CL (2003) Antimicrobial peptides as effector molecules of mammalian host defense. Contrib Microbiol 10:106–148

    Article  CAS  PubMed  Google Scholar 

  • Bevins CL, Salzman NH (2011) Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 9:356–368

    Article  CAS  PubMed  Google Scholar 

  • Bevins CL, Stange EF, Wehkamp J (2009) Decreased Paneth cell defensin expression in ileal Crohn’s disease is independent of inflammation, but linked to the NOD2 1007fs genotype. Gut 58:882–883

    CAS  PubMed  Google Scholar 

  • Bik EM, Eckburg PB, Gill SR, Nelson KE, Purdom EA, Francois F, Perez-Perez G, Blaser MJ, Relman DA (2006) Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U S A 103:732–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bik EM, Long CD, Armitage GC, Loomer P, Emerson J, Mongodin EF, Nelson KE, Gill SR, Fraser-Liggett CM, Relman DA (2010) Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J 4:962–974

    Article  PubMed  PubMed Central  Google Scholar 

  • Boman HG (2003) Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215

    Article  CAS  PubMed  Google Scholar 

  • Brinkmann V, Zychlinsky A (2007) Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 5:577–582

    Article  CAS  PubMed  Google Scholar 

  • Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456:259–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cario E (2010) Toll-like receptors in inflammatory bowel diseases: a decade later. Inflamm Bowel Dis 16:1583–1597

    Article  PubMed  PubMed Central  Google Scholar 

  • Celli JP, Turner BS, Afdhal NH, Keates S, Ghiran I, Kelly CP, Ewoldt RH, McKinley GH, So P, Erramilli S, Bansil R (2009) Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc Natl Acad Sci U S A 106:14321–14326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, Winter MG, Winter SE, Wehkamp J, Shen B, Salzman NH, Underwood MA, Tsolis RM, Young GM, Lu W, Lehrer RI, Baumler AJ, Bevins CL (2012) Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337:477–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clevers HC, Bevins CL (2013) Paneth cells: maestros of the small intestinal crypts. Annu Rev Physiol 75:289–311

    Article  CAS  PubMed  Google Scholar 

  • David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563

    Article  CAS  PubMed  Google Scholar 

  • Dixon LJ, Kabi A, Nickerson KP, McDonald C (2015) Combinatorial effects of diet and genetics on inflammatory bowel disease pathogenesis. Inflamm Bowel Dis 21(4):912–922

    Article  PubMed  PubMed Central  Google Scholar 

  • Doss M, White MR, Tecle T, Gantz D, Crouch EC, Jung G, Ruchala P, Waring AJ, Lehrer RI, Hartshorn KL (2009) Interactions of alpha-, beta-, and theta-defensins with influenza A virus and surfactant protein D. J Immunol 182:7878–7887

    Article  CAS  PubMed  Google Scholar 

  • Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Buschenfelde KH (1995) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 102:448–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellinghaus D, Bethune J, Petersen BS, Franke A (2015) The genetics of Crohn’s disease and ulcerative colitis–status quo and beyond. Scand J Gastroenterol 50:13–23

    Article  CAS  PubMed  Google Scholar 

  • Ericksen B, Wu Z, Lu W, Lehrer RI (2005) Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother 49:269–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, Shimoda S, Iwasaki H, Shimono N, Ayabe T, Akashi K, Teshima T (2012) Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha-defensins. Blood 120:223–231

    Article  CAS  PubMed  Google Scholar 

  • Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, Reinisch W, Teml A, Schwab M, Lichter P, Radlwimmer B, Stange EF (2006) A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 79:439–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fillon SA, Harris JK, Wagner BD, Kelly CJ, Stevens MJ, Moore W, Fang R, Schroeder S, Masterson JC, Robertson CE, Pace NR, Ackerman SJ, Furuta GT (2012) Novel device to sample the esophageal microbiome–the esophageal string test. PLoS One 7:e42938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17:179–184

    Article  PubMed  Google Scholar 

  • Gersemann M, Becker S, Kubler I, Koslowski M, Wang G, Herrlinger KR, Griger J, Fritz P, Fellermann K, Schwab M, Wehkamp J, Stange EF (2009) Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation 77:84–94

    Article  CAS  PubMed  Google Scholar 

  • Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL (2002) Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 3:583–590

    Article  CAS  PubMed  Google Scholar 

  • Girardin SE, Hugot JP, Sansonetti PJ (2003) Lessons from Nod2 studies: towards a link between Crohn’s disease and bacterial sensing. Trends Immunol 24:652–658

    Article  CAS  PubMed  Google Scholar 

  • Goel A, Boland CR (2010) Recent insights into the pathogenesis of colorectal cancer. Curr Opin Gastroenterol 26:47–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJ (2006) Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 44:4136–4141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grigat J, Soruri A, Forssmann U, Riggert J, Zwirner J (2007) Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 179:3958–3965

    Article  CAS  PubMed  Google Scholar 

  • Gruenheid S, Le MH (2012) Resistance to antimicrobial peptides in Gram-negative bacteria. FEMS Microbiol Lett 330:81–89

    Article  CAS  PubMed  Google Scholar 

  • Hanage WP (2014) Microbiology: microbiome science needs a healthy dose of scepticism. Nature 512:247–248

    Article  CAS  PubMed  Google Scholar 

  • Hans M, Madaan HV (2014) Epithelial antimicrobial peptides: guardian of the oral cavity. Int J Pept 2014:370297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM (2012) ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487:477–481

    Article  CAS  PubMed  Google Scholar 

  • Heitman DW, Pool TB, Cameron IL (1980) Changes in proliferation and surface morphology in the rat ileum in response to total parenteral nutrition. J Anat 130:603–615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Helander HF, Fandriks L (2014) Surface area of the digestive tract – revisited. Scand J Gastroenterol 49:681–689

    Article  PubMed  Google Scholar 

  • Hodin CM, Lenaerts K, Grootjans J, de Haan JJ, Hadfoune M, Verheyen FK, Kiyama H, Heineman E, Buurman WA (2011) Starvation compromises Paneth cells. Am J Pathol 179:2885–2893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hooper LV, Gordon JI (2001) Commensal host-bacterial relationships in the gut. Science 292(5519):1115–1118

    Article  CAS  PubMed  Google Scholar 

  • Hosaka Y, Koslowski M, Nuding S, Wang G, Schlee M, Schafer C, Saigenji K, Stange EF, Wehkamp J (2008) Antimicrobial host defense in the upper gastrointestinal tract. Eur J Gastroenterol Hepatol 20:1151–1158

    Article  CAS  PubMed  Google Scholar 

  • Hugot J-P, Chamaillard C, Zouali H, Lesage S, Cezard J-P, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel J-F, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  CAS  PubMed  Google Scholar 

  • Jaeger SU, Schroeder BO, Meyer-Hoffert U, Courth L, Fehr SN, Gersemann M, Stange EF, Wehkamp J (2013) Cell-mediated reduction of human beta-defensin 1: a major role for mucosal thioredoxin. Mucosal Immunol 6(6):1179–1190

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ji Y, Sun S, Goodrich JK, Kim H, Poole AC, Duhamel GE, Ley RE, Qi L (2014) Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice. Cell Rep 8:137–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johansson ME, Larsson JM, Hansson GC (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U S A 108(Suppl 1):4659–4665

    Article  CAS  PubMed  Google Scholar 

  • Johansson ME, Sjovall H, Hansson GC (2013) The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10:352–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kavanagh K, Dowd S (2004) Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 56:285–289

    Article  CAS  PubMed  Google Scholar 

  • Kiehne K, Brunke G, Meyer D, Harder J, Herzig KH (2005) Oesophageal defensin expression during Candida infection and reflux disease. Scand J Gastroenterol 40:501–507

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734

    Article  CAS  PubMed  Google Scholar 

  • Koon HW, Shih DQ, Chen J, Bakirtzi K, Hing TC, Law I, Ho S, Ichikawa R, Zhao D, Xu H, Gallo R, Dempsey P, Cheng G, Targan SR, Pothoulakis C (2011) Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology 141:1852–1863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koprivnjak T, Peschel A (2011) Bacterial resistance mechanisms against host defense peptides. Cell Mol Life Sci 68:2243–2254

    Article  CAS  PubMed  Google Scholar 

  • Koslowski MJ, Kubler I, Chamaillard M, Schaeffeler E, Reinisch W, Wang G, Beisner J, Teml A, Peyrin-Biroulet L, Winter S, Herrlinger KR, Rutgeerts P, Vermeire S, Cooney R, Fellermann K, Jewell D, Bevins CL, Schwab M, Stange EF, Wehkamp J (2009) Genetic variants of Wnt transcription factor TCF-4 (TCF7L2) putative promoter region are associated with small intestinal Crohn’s disease. PLoS One 4:e4496

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koslowski MJ, Teltschik Z, Beisner J, Schaeffeler E, Wang G, Kubler I, Gersemann M, Cooney R, Jewell D, Reinisch W, Vermeire S, Rutgeerts P, Schwab M, Stange EF, Wehkamp J (2012) Association of a functional variant in the Wnt co-receptor LRP6 with early onset ileal Crohn’s disease. PLoS Genet 8:e1002523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubler I, Koslowski MJ, Gersemann M, Fellermann K, Beisner J, Becker S, Rothfuss K, Herrlinger KR, Stange EF, Wehkamp J (2009) Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn’s disease. Aliment Pharmacol Ther 30(6):621–633

    Article  CAS  PubMed  Google Scholar 

  • Kudryashova E, Quintyn R, Seveau S, Lu W, Wysocki VH, Kudryashov DS (2014) Human defensins facilitate local unfolding of thermodynamically unstable regions of bacterial protein toxins. Immunity 41:709–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kyo K, Parkes M, Takei Y, Nishimori H, Vyas P, Satsangi J, Simmons J, Nagawa H, Baba S, Jewell D, Muto T, Lathrop GM, Nakamura Y (1999) Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3. Hum Mol Genet 8:307–311

    Article  CAS  PubMed  Google Scholar 

  • Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S (2003) Crohn’s disease and the NOD2 gene: a role for paneth cells. Gastroenterology 125:47–57

    Article  CAS  PubMed  Google Scholar 

  • Le BN, Heresbach D, Kerbaol M, Caulet S, Bretagne JF, Chaperon J, Gosselin M, Ramee MP (1995) Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis. J Clin Pathol 48:749–753

    Article  Google Scholar 

  • MacPherson A, Khoo UY, Forgacs I, Philpott-Howard J, Bjarnason I (1996) Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut 38:365–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchesi JR, Dutilh BE, Hall N, Peters WH, Roelofs R, Boleij A, Tjalsma H (2011) Towards the human colorectal cancer microbiome. PLoS One 6:e20447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh PD (2006) Dental plaque as a biofilm and a microbial community – implications for health and disease. BMC Oral Health (6 Suppl 1):S14

    Google Scholar 

  • Matsuoka K, Kanai T (2015) The gut microbiota and inflammatory bowel disease. Semin Immunopathol 37:47–55

    Article  CAS  PubMed  Google Scholar 

  • McGee DJ, George AE, Trainor EA, Horton KE, Hildebrandt E, Testerman TL (2011) Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37. Antimicrob Agents Chemother 55:2897–2904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melino S, Santone C, Di NP, Sarkar B (2014) Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. FEBS J 281:657–672

    Article  CAS  PubMed  Google Scholar 

  • Moehle C, Ackermann N, Langmann T, Aslanidis C, Kel A, Kel-Margoulis O, Schmitz-Madry A, Zahn A, Stremmel W, Schmitz G (2006) Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. J Mol Med (Berl) 84:1055–1066

    Article  CAS  Google Scholar 

  • Mondel M, Schroeder BO, Zimmermann K, Huber H, Nuding S, Beisner J, Fellermann K, Stange EF, Wehkamp J (2008) Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans. Mucosal Immunol 2:166–172

    Article  PubMed  CAS  Google Scholar 

  • Nuding S, Fellermann K, Wehkamp J, Stange EF (2007) Reduced mucosal antimicrobial activity in Crohn’s disease of the colon. Gut 56:1240–1247

    Article  PubMed  PubMed Central  Google Scholar 

  • Nuding S, Gersemann M, Hosaka Y, Konietzny S, Schaefer C, Beisner J, Schroeder BO, Ostaff MJ, Saigenji K, Ott G, Schaller M, Stange EF, Wehkamp J (2013) Gastric antimicrobial peptides fail to eradicate Helicobacter pylori infection due to selective induction and resistance. PLoS One 8:e73867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odze R (2003) Diagnostic problems and advances in inflammatory bowel disease. Mod Pathol 16:347–358

    Article  PubMed  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karalluskas R, Duerr RH, Achkar J-P, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  CAS  PubMed  Google Scholar 

  • Ohigashi S, Sudo K, Kobayashi D, Takahashi O, Takahashi T, Asahara T, Nomoto K, Onodera H (2013) Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. Dig Dis Sci 58(6):1717–1726

    Article  CAS  PubMed  Google Scholar 

  • Ostaff MJ, Stange EF, Wehkamp J (2013) Antimicrobial peptides and gut microbiota in homeostasis and pathology. EMBO Mol Med 5:1465–1483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ouellette AJ, Bevins CL (2001) Paneth cell defensins and innate immunity of the small bowel. Inflamm Bowel Dis 7:43–50

    Article  CAS  PubMed  Google Scholar 

  • Pahl et al (2011) IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis. Am J Physiol Gastrointest Liver Physiol. 2011;300(4):G547–553. http://www.ncbi.nlm.nih.gov/pubmed/?term=Pahl+defensin+2011. doi: 10.1152/ajpgi.00251.2010. Epub 2011 Jan 13.

    Google Scholar 

  • Peyrin-Biroulet L, Beisner J, Wang G, Nuding S, Oommen ST, Kelly D, Parmentier-Decrucq E, Dessein R, Merour E, Chavatte P, Grandjean T, Bressenot A, Desreumaux P, Colombel JF, Desvergne B, Stange EF, Wehkamp J, Chamaillard M (2010) Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci U S A 107:8772–8777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rohrl J, Geissler EK, Hehlgans T (2012a) Friend or foe: a novel role of beta-defensins in tumor development. Oncoimmunology 1:1159–1160

    Article  PubMed  PubMed Central  Google Scholar 

  • Rohrl J, Huber B, Koehl GE, Geissler EK, Hehlgans T (2012b) Mouse beta-defensin 14 (Defb14) promotes tumor growth by inducing angiogenesis in a CCR6-dependent manner. J Immunol 188:4931–4939

    Article  PubMed  CAS  Google Scholar 

  • Rumio C, Besusso D, Palazzo M, Selleri S, Sfondrini L, Dubini F, Menard S, Balsari A (2004) Degranulation of paneth cells via toll-like receptor 9. Am J Pathol 165:373–381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saleh M, Trinchieri G (2011) Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat Rev Immunol 11:9–20

    Article  CAS  PubMed  Google Scholar 

  • Salzman NH, Gottsch JD, Huttner KM, Paterson Y, Bevins CL (2003) Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature advance online publication. 19-3-2003. Ref Type: Magazine Article

    Google Scholar 

  • Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, Amir E, Teggatz P, Barman M, Hayward M, Eastwood D, Stoel M, Zhou Y, Sodergren E, Weinstock GM, Bevins CL, Williams CB, Bos NA (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11:76–83

    Article  CAS  PubMed  Google Scholar 

  • Samaranayake LP, Keung LW, Jin L (2009) Oral mucosal fungal infections. Periodontol 2000 49:39–59

    Article  PubMed  Google Scholar 

  • Samaranayake YH, Samaranayake LP, Pow EH, Beena VT, Yeung KW (2001) Antifungal effects of lysozyme and lactoferrin against genetically similar, sequential Candida albicans isolates from a human immunodeficiency virus-infected southern Chinese cohort. J Clin Microbiol 39:3296–3302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sartor RB (2001) Intestinal microflora in human and experimental inflammatory bowel disease. Curr Opin Gastroenterol 17:324–330

    Article  CAS  PubMed  Google Scholar 

  • Sartor RB (2014) The intestinal microbiota in inflammatory bowel diseases. Nestle Nutr Inst Workshop Ser 79:29–39

    Article  PubMed  Google Scholar 

  • Saulnier DM, Kolida S, Gibson GR (2009) Microbiology of the human intestinal tract and approaches for its dietary modulation. Curr Pharm Des 15:1403–1414

    Article  CAS  PubMed  Google Scholar 

  • Schauber J, Rieger D, Weiler F, Wehkamp J, Eck M, Fellermann K, Scheppach W, Gallo RL, Stange EF (2006) Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 18:615–621

    Article  CAS  PubMed  Google Scholar 

  • Schlee M, Harder J, Koten B, Stange EF, Wehkamp J, Fellermann K (2008) Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol 151:528–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlee M, Wehkamp J, Altenhoefer A, Oelschlaeger TA, Stange EF, Fellermann K (2007) The induction of human beta-defensin-2 by the probiotic escherichia coli nissle 1917 is mediated through flagellin. Infect Immun 75(5):2399–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroeder BO, Ehmann D, Precht JC, Castillo PA, Kuchler R, Berger J, Schaller M, Stange EF, Wehkamp J (2015) Paneth cell alpha-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal Immunol 8(3):661–671

    Article  CAS  PubMed  Google Scholar 

  • Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469:419–423

    Article  CAS  PubMed  Google Scholar 

  • Sears CL (2005) A dynamic partnership: celebrating our gut flora. Anaerobe 11:247–251

    Article  PubMed  Google Scholar 

  • Sekirov I, Russell SL, Antunes LC, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904

    Article  CAS  PubMed  Google Scholar 

  • Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557

    Article  CAS  PubMed  Google Scholar 

  • Semple F, MacPherson H, Webb S, Cox SL, Mallin LJ, Tyrrell C, Grimes GR, Semple CA, Nix MA, Millhauser GL, Dorin JR (2011) Human beta-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF. Eur J Immunol 41:3291–3300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Semple F, Webb S, Li HN, Patel HB, Perretti M, Jackson IJ, Gray M, Davidson DJ, Dorin JR (2010) Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol 40:1073–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shanahan MT, Carroll IM, Grossniklaus E, White A, von Furstenberg RJ, Barner R, Fodor AA, Henning SJ, Sartor RB, Gulati AS (2014) Mouse Paneth cell antimicrobial function is independent of Nod2. Gut 63(6):903–910

    Article  CAS  PubMed  Google Scholar 

  • Shen B, Porter EM, Reynoso E, Shen C, Ghosh D, Connor JT, Drazba J, Rho HK, Gramlich TL, Li R, Ormsby AH, Sy MS, Ganz T, Bevins CL (2005) Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract. J Clin Pathol 58:687–694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Van Tran NJ, Furet JP (2011) Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 6:e16393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sommer F, Backhed F (2013) The gut microbiota–masters of host development and physiology. Nat Rev Microbiol 11:227–238

    Article  CAS  PubMed  Google Scholar 

  • Stilling RM, Bordenstein SR, Dinan TG, Cryan JF (2014) Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front Cell Infect Microbiol 4:147

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun J, Hobert ME, Rao AS, Neish AS, Madara JL (2004) Bacterial activation of beta-catenin signaling in human epithelia. Am J Physiol Gastrointest Liver Physiol 287:G220–G227

    Article  CAS  PubMed  Google Scholar 

  • Swidergall M, Ernst JF (2014) Interplay between Candida albicans and the antimicrobial peptide armory. Eukaryot Cell 13:950–957

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tai EK, Wu WK, Wang XJ, Wong HP, Yu L, Li ZJ, Lee CW, Wong CC, Yu J, Sung JJ, Gallo RL, Cho CH (2013) Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp(−/−) mice. Gene Ther 20:187–193

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9

    Article  CAS  PubMed  Google Scholar 

  • Tan G, Li RH, Li C, Wu F, Zhao XM, Ma JY, Lei S, Zhang WD, Zhi FC (2015a) Down-regulation of human enteric antimicrobial peptides by NOD2 during differentiation of the paneth cell lineage. Sci Rep 5:8383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan G, Zeng B, Zhi FC (2015b) Regulation of human enteric alpha-defensins by NOD2 in the Paneth cell lineage. Eur J Cell Biol 94:60–66

    Article  CAS  PubMed  Google Scholar 

  • Teltschik Z, Wiest R, Beisner J, Nuding S, Hofmann C, Schoelmerich J, Bevins CL, Stange EF, Wehkamp J (2012) Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense. Hepatology 55(4):1154–1163

    Article  PubMed  Google Scholar 

  • Thachil E, Hugot JP, Arbeille B, Paris R, Grodet A, Peuchmaur M, Codogno P, Barreau F, Ogier-Denis E, Berrebi D, Viala J (2012) Abnormal activation of autophagy-induced crinophagy in paneth cells from patients with Crohn’s disease. Gastroenterology 142:1097–1099

    Article  PubMed  Google Scholar 

  • Thompson GR, Trexler PC (1971) Gastrointestinal structure and function in germ-free or gnotobiotic animals. Gut 12:230–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomalka J, Azodi E, Narra HP, Patel K, O’Neill S, Cardwell C, Hall BA, Wilson JM, Hise AG (2015) Beta-defensin 1 plays a role in acute mucosal defense against Candida albicans. J Immunol 194:1788–1795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trautwein-Weidner K, Gladiator A, Nur S, Diethelm P, LeibundGut-Landmann S (2015) IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils. Mucosal Immunol 8:221–231

    Article  CAS  PubMed  Google Scholar 

  • Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484

    Article  CAS  PubMed  Google Scholar 

  • Uraki S, Sugimoto K, Shiraki K, Tameda M, Inagaki Y, Ogura S, Kasai C, Nojiri K, Yoneda M, Yamamoto N, Takei Y, Nobori T, Ito M (2014) Human beta-defensin-3 inhibits migration of colon cancer cells via downregulation of metastasis-associated 1 family, member 2 expression. Int J Oncol 45:1059–1064

    CAS  PubMed  Google Scholar 

  • Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C (2009) Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 4:e6026

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van ’t Hof W, Veerman EC, Nieuw Amerongen AV, Ligtenberg AJ (2014) Antimicrobial defense systems in saliva. Monogr Oral Sci 24:40–51

    Article  Google Scholar 

  • Voreades N, Kozil A, Weir TL (2014) Diet and the development of the human intestinal microbiome. Front Microbiol 5:494

    Article  PubMed  PubMed Central  Google Scholar 

  • Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, Petrovska L (2011) High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 11:7

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang P, Duan D, Zhou X, Li X, Yang J, Deng M, Xu Y (2015) Relationship between expression of human gingival beta-defensins and levels of periodontopathogens in subgingival plaque. J Periodontal Res 50:113–122

    Article  CAS  PubMed  Google Scholar 

  • Wang ZK, Yang YS (2013) Upper gastrointestinal microbiota and digestive diseases. World J Gastroenterol 19:1541–1550

    Article  PubMed  PubMed Central  Google Scholar 

  • Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K, Schroeder JM, Stange EF (2003) Inducible and constitutive beta-defensins are differentially expressed in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 9:215–223

    Article  PubMed  Google Scholar 

  • Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, Schroder JM, Bevins CL, Fellermann K, Stange EF (2004) NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal alpha-defensin expression. Gut 53:1658–1664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H Jr, Fellermann K, Ganz T, Stange EF, Bevins CL (2005) Reduced Paneth cell alpha-defensins in ileal Crohn’s disease. Proc Natl Acad Sci U S A 102:18129–18134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wehkamp J, Schwind B, Herrlinger KR, Baxmann S, Schmidt K, Duchrow M, Wohlschlager C, Feller AC, Stange EF, Fellermann K (2002) Innate immunity and colonic inflammation: enhanced expression of epithelial alpha-defensins. Dig Dis Sci 47:1349–1355

    Article  CAS  PubMed  Google Scholar 

  • Wehkamp J, Wang G, Kubler I, Nuding S, Gregorieff A, Schnabel A, Kays RJ, Fellermann K, Burk O, Schwab M, Clevers H, Bevins CL, Stange EF (2007) The Paneth cell alpha-defensin deficiency of ileal Crohn’s disease is linked to Wnt/Tcf-4. J Immunol 179:3109–3118

    Article  CAS  PubMed  Google Scholar 

  • Wenzel UA, Magnusson MK, Rydstrom A, Jonstrand C, Hengst J, Johansson ME, Velcich A, Ohman L, Strid H, Sjovall H, Hansson GC, Wick MJ (2014) Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis. PLoS One 9:e100217

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–117

    Article  CAS  PubMed  Google Scholar 

  • Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dr. Margarete Fischer Bosch Institute of clinical pharmacology and University of Tübingen, Tübingen , Germany

    Maureen J. Ostaff

  2. Department of Gastroenterology, Robert Bosch Hospital, Stuttgart, Germany

    Eduard F. Stange

  3. Department of Internal Medicine I, University Hospital Tuebingen, Otfried-Müller-Straße 10, Tuebingen, 72076, Germany

    Jan Wehkamp

Authors
  1. Maureen J. Ostaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduard F. Stange
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Wehkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Wehkamp .

Editor information

Editors and Affiliations

  1. Department of Dermatology, University-Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Jürgen Harder

  2. Department of Dermatology, University-Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Jens-M. Schröder

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ostaff, M.J., Stange, E.F., Wehkamp, J. (2016). Antimicrobial Peptides in the Gut. In: Harder, J., Schröder, JM. (eds) Antimicrobial Peptides. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-24199-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation