Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-10T22:19:39.651Z Has data issue: false hasContentIssue false

Mucosal bacteria in ulcerative colitis

Published online by Cambridge University Press:  08 March 2007

S. Macfarlane*
Affiliation:
Microbiology and Gut Biology Group, University of Dundee, Dundee, DD1 9SY, UK
E. Furrie
Affiliation:
Microbiology and Gut Biology Group, University of Dundee, Dundee, DD1 9SY, UK
A. Kennedy
Affiliation:
Microbiology and Gut Biology Group, University of Dundee, Dundee, DD1 9SY, UK
J. H. Cummings
Affiliation:
Division of Pathology and Neuroscience, University of Dundee, Dundee, DD1 9SY, UK
G. T. Macfarlane
Affiliation:
Microbiology and Gut Biology Group, University of Dundee, Dundee, DD1 9SY, UK
*
*Corresponding author: Dr S. Macfarlane, fax +44 1382 633952, email s.macfarlane@dundee.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease of unknown aetiology, although bacterial species belonging to the normal colonic microbiota are known to be involved in its initiation and maintenance. Several organisms have been linked to the disease; however, mucosa-associated bacteria are more likely to be involved than their luminal counterparts, due to their close proximity to the host epithelium. Comparative bacteriological analyses were done on rectal biopsies to investigate differences in mucosal bacteria in patients with UC and healthy controls. Complex bacterial communities were found in both groups, with significant reductions in bifidobacterial numbers in UC, which suggested that they might have a protective role in the disease. Accordingly, a therapy for treating UC was designed, with the aim of modifying the mucosal microbiota to increase bifidobacterial colonisation and reduce inflammation. Ranges of mucosal and faecal bifidobacteria were tested for their substrate preferences and their abilities to survive under a variety of environmental conditions. A synbiotic comprising a probiotic (Bifidobacterium longum) isolated from healthy rectal mucosa combined with a prebiotic (oligofructose-enriched inulin – Synergy 1TM) was developed. The treatment was used in a randomised controlled trial involving eighteen patients with active UC, for a period of 1 month. Rectal biopsies were collected at the beginning and end of the study. Bacteriological analysis and transcription levels of epithelium-related immune markers were assessed. Results demonstrated that short-term synbiotic treatment resulted in increased bifidobacterial colonisation of the rectal mucosa and induced significant reductions in the expression of molecules that control inflammation in active UC.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

Anwar, H, Dasgupta, MK & Costerton, JW (1990) Testing the susceptibility of bacteria in biofilms to antibacterial agents. Antimicrob Agents Chemother 34, 20432046.Google Scholar
Balish, E & Warner, T (2002) Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol 160, 22532257.CrossRefGoogle ScholarPubMed
Bamba, T, Matsuda, H, Endo, M & Fujiyama, Y (1995) The pathogenic role of Bacteroides vulgatus in patients with ulcerative colitis. J Gastroenterol 30 Suppl. 8, 4547.Google Scholar
Borruel, N, Carol, M, Casallas, F, Antolin, M, de Lara, F, Espin, E, Naval, J, Guarner, F & Malagelada, JR (2002) Increased mucosal tumour necrosis factor α production in Crohn's disease can be down regulated ex vivo by probiotic bacteria. Gut 51, 659664.Google Scholar
Burke, D & Axon, A (1988) Adhesive E. coli in inflammatory bowel disease and infective diarrhoea. Br Med J 297, 102104.Google Scholar
Butcher, EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67, 10331036.Google Scholar
Campieri, M & Gionchetti, P (2001) Bacteria as the cause of ulcerative colitis. Gut 48, 132135.CrossRefGoogle ScholarPubMed
Chadwick, VS (1991) Etiology of chronic ulcerative colitis and Crohn's disease. In The Large Intestine: Physiology, Pathophysiology and Disease, pp. 445463 [Phillips, SF, Pemberton, JH and Shorter, RG, editors]. New York: Raven Press.Google Scholar
Cummings, JH, Macfarlane, GT & Macfarlane, S (2003) Intestinal bacteria and ulcerative colitis. Curr Issues Intest Microbiol 4, 920.Google ScholarPubMed
Daig, R, Rogler, G, Aschenbrenner, E, Vogl, D, Falk, W, Gross, V, Scholmerich, J & Andus, T (2000) Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6. Gut 46, 350358.Google Scholar
Duchman, R, Kaiser, I, Hermann, E, Mayet, W, Ewe, K, Meyer Zum, KH (1995) Tolerance exists towards resident intestinal flora but is broken down in active inflammatory bowel disease (IBD). Clin Exp Immunol 102, 448455.Google Scholar
Fabia, R, Ar'Rajab, A, Johansson, ML, Willen, R, Molin, G & Bengmark, S (1993a) The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat. Scand J Gastroenterol 28, 155162.CrossRefGoogle ScholarPubMed
Fabia, R, Ar'Rajab, A, Johansson, ML, Andersson, R, Willen, R, Jeppsson, B, Molin, G & Bengmark, S (1993b) Impairment of bacterial flora in human ulcerative colitis and experimental colitis in the rat. Digestion 54, 248255.CrossRefGoogle ScholarPubMed
Farina, C, Arosio, M, Mangia, M & Moioli, F (2001) Lactobacillus casei subsp. rhamnosus sepsis in a patient with ulcerative colitis. J Clin Gastroenterol 33, 251252.Google Scholar
Fellerman, K, Wehkamp, J, Herrlinger, KR & Stange, EF (2003) Crohn's disease: a defensin deficiency syndrome?. Eur J Gastroenterol Hepatol 15, 627634.CrossRefGoogle Scholar
Furrie, E, Macfarlane, S, Cummings, JH & Macfarlane, GT (2004) Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response. Gut 53, 9299.Google Scholar
Furrie, E, Macfarlane, S, Kennedy, A, Cummings, JH, Walsh, SV, O'Neil, DA & Macfarlane, GT (2005) Synbiotic therapy ( Bifidobacterium longum /Synergy 1 TM ) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 242249.Google Scholar
Gibson, GR & Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota introducing the concept of prebiotics. J Nutr 125, 14011412.Google Scholar
Gionchetti, P, Rizzello, F, Venturi, A, Brigidi, P, Matteuzzi, D, Bazzocchi, G, Poggioli, G, Miglioli, M & Campieri, M (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119, 305309.Google Scholar
Guslandi, M, Mezzi, G, Sorghi, M & Testoni, PA (2000) Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis Sci 45, 14621464.CrossRefGoogle ScholarPubMed
Hartley, MG, Hudson, MJ, Swarbrick, ET, Gent, AE, Hellier, MD & Grace, RH (1993) Adhesive and hydrophobic properties of Escherichia coli from the rectal mucosa of patients with ulcerative colitis. Gut 34, 6367.Google Scholar
He, F, Tuomola, E, Arvilommi, H & Seppo, S (2000) Modulation of humoral immune response through probiotic intake. FEMS Immunol Med Microbiol 29, 4752.Google Scholar
Hill, MJ (1986) The possible role of bacteria in inflammatory bowel disease. Curr Concepts Gastroenterol 3, 1014.Google Scholar
Ibnou-Zekri, N, Blum, S, Schiffrin, EJ, von der Weid, T (2003) Divergent patterns of colonization and immune response elicited from two intestinal Lactobacillus strains that display similar properties in vitro. Infect Immun 71, 428436.CrossRefGoogle ScholarPubMed
Kruis, W, Schutz, Fric P, Fixa, B, Judmaier, G, Stolte, M (1997) Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission in ulcerative colitis. Aliment Pharmacol Ther 11, 853858.CrossRefGoogle ScholarPubMed
Maassen, CB, van Holten-Neelen, C, Balk, F, den Bak-Glashouwer, MJ, Leer, RJ, Lamen, JD, Boersma, WJ & Claassen, E (2000) Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains. Vaccine 18, 26132623.Google Scholar
Macdonald, TT, Monteleone, G & Pender, SLF (2000) Recent developments in the immunology of inflammatory bowel disease. Scand J Immunol 51, 29.CrossRefGoogle ScholarPubMed
Macfarlane, GT & Cummings, JH (2002) Probiotics, infection and immunity. Curr Opin Infect Dis 15, 501506.Google Scholar
Macfarlane, S, Cummings, JH & Macfarlane, GT (1999) Bacterial colonisation of surfaces in the large intestine. In Colonic Microflora, Nutrition and Health, pp. 7187 [Gibson, GR and Roberfroid, M, editors] London: Chapman & Hall.CrossRefGoogle Scholar
Macfarlane, S, Hopkins, MJ & Macfarlane, GT (2000) Bacterial growth and metabolism on surfaces in the large intestine. Microb Ecol Health Dis 2, 6472.Google Scholar
Macfarlane, S, Furrie, E, Cummings, JH & Macfarlane, GT (2004) Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis. Clin Infect Dis 38, 16901699.CrossRefGoogle ScholarPubMed
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, 365375.Google Scholar
Madsen, KL, Doyle, JS, Jewell, LD, Tavernini, MM & Fedorak, RN (1999) Lactobacillus species prevent colitis in interleukin 10 gene-deficient mice. Gastroenterology 116, 11071114.Google Scholar
Mao, Y, Nobaek, S, Kasravi, B, Adawi, D, Stenram, U, Molin, G & Jeppsson, B (1996) The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats. Gastroenterology 111, 334344.Google Scholar
Matsuda, H, Fujiyama, Y, Andoh, A, Ushijima, T, Kajinami, T & Bamba, T (2000) Characterization of antibody responses against rectal mucosa-associated bacterial flora in patients with ulcerative colitis. J Gastroenterol Hepatol 15, 6168.Google Scholar
Monteiro, E, Fossey, J, Shiner, M, Draser, BS & Allison, AC (1971) Antibacterial antibodies in rectal and colonic mucosa in ulcerative colitis. Lancet 1, 249251.CrossRefGoogle ScholarPubMed
Navarro, F & Hanauer, SB (2003) Treatment of inflammatory bowel disease: safety and tolerability issues. Am J Gastroenterol 98, S18S23.CrossRefGoogle Scholar
Niness, KR (1999) Inulin and oligofructose: what are they?. British J Nutr 129, Suppl. 7, 1402S1406S.Google Scholar
Onderdonk, AB (1983) Role of the intestinal microflora in ulcerative colitis. in Human Intestinal Microflora in Health and Disease, 481493 [Hentges, DJ, editors]. New York: Academic Press.Google Scholar
Onderdonk, AB & Bartlett, MD (1979) Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr 32, 258265.Google Scholar
O'Neil, DA (2003) Regulation of expression of beta-defensins: endogenous enteric peptide antibiotics. Mol Immunol 40, 445450.CrossRefGoogle ScholarPubMed
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, 67186724.Google Scholar
Ott, SJ, Musfeldt, M, Wendererorh, DF, Hampe, J, Brant, O, Folsch, UR, Timmis, KN & Schrieiber, S (2004) Reduction in diversity of the colonic mucosa associated microflora in patients with active inflammatory bowel disease. Gut 53, 685693.CrossRefGoogle ScholarPubMed
Pathmakanthan, S, Thornley, JP & Hawkey, CJ (1999) Mucosally associated bacterial flora of the human colon: quantitative and species specific differences between normal and inflammed colonic biopsies. Microb Ecol Health Dis 11, 169174.Google Scholar
Poxton, IR, Brown, R, Sawyerr, A & Ferguson, A (1997) Mucosa-associated bacterial flora of the human colon. J Med Microbiol 46, 8591.CrossRefGoogle ScholarPubMed
Rembacken, BJ, Snelling, AM, Hawkey, PM, Chalmers, DM & Axon, ATR (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354, 636639.Google Scholar
Ruseler, van, Embden, JGH, Schouten, WR, Van Lieshout, LMC (1994) Pouchitis: result of microbial imbalance?. Gut 35, 658664.Google Scholar
Sadlack, B, Merz, H & Schorle, H (1993) Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 175, 253261.CrossRefGoogle Scholar
Sartor, RB, Rath, HC & Sellon, HK (1996) Microbial factors in chronic intestinal inflammation. Curr Opin Gastroenterol 12, 327333.CrossRefGoogle Scholar
Schultsz, C, Moussa, M, van Ketel, R, Tytgat, GN & Dankert, J (1997) Frequency of pathogenic and enteroadherent Escherichia coli in patients with inflammatory bowel disease and controls. J Clin Pathol 50, 573579.CrossRefGoogle ScholarPubMed
Schultsz, C, Van der Berg, FM, ten Kate, FW, Tytgat, GN & Dankert, J (1999) The intestinal mucous layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology 117, 10891097.Google Scholar
Schultz, M, Veltkamp, C & Dieleman, LA (2002) Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm Bowel Dis 8, 7180.CrossRefGoogle ScholarPubMed
Seksik, P, Rigottier-Gois, L, Gramet, G, Sutren, M, Pochart, P, Marteau, P, Jian, R & Dore, J (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 52, 237242.Google Scholar
Shanahan, F & McCarthy, J (2000) Functional foods and prebiotics – time for gastroenterologists to embrace the concepts. Curr Gastroenterol Rep 2, 345346.Google Scholar
Steidler, L, Hans, W, Schotte, L, Neirynck, S, Obermeier, F, Falk, W, Fiers, W & Remaut, E (2000) Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289, 13521355.CrossRefGoogle Scholar
Swidsinski, A, Ladhoff, A & Pernthaler, A (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122, 4454.Google Scholar
Taurog, JD, Richardson, JA, Croft, JT, Simmons, WA, Zhou, M, Fernandez-Sueiro, JL, Balish, E & Hammer, RE (1994) The germ free state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180, 23592364.Google Scholar
Tvede, M, Bondesen, S, Nielsen, OH & Rasmussen, SN (1983) Serum antibodies to Bacteroides species in chronic inflammatory bowel disease. Scand J Gastroenterol 18, 783789.CrossRefGoogle ScholarPubMed
Van der Waaij, D, Cohen, BJ & Anver, MR (1974) Mitigation of experimental inflammatory bowel disease in guinea pigs by selective elimination of the aerobic gram-negative intestinal microflora. Gastroenterology 67, 460472.Google Scholar
Van der Wiel-Korstanje, J & Winkler, K (1975) The faecal flora in ulcerative colitis. J Med Microbiol 8, 491501.Google Scholar
Venturi, A, Gionchetti, P, Rizzello, F, Johansson, R, Zucconi, E, Brigidi, P, Matteuzzi, D & Campiere, M (1999) Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 13, 11031108.Google Scholar
Von Wulffen, H, Russmann, H, Karch, H, Meyer, T, Bitzan, M, Kohrt, TC & Aleksic, S (1989) Verocytotoxin-producing Escherichia coli O2:H5 isolated from patients with ulcerative colitis. Lancet 1, 14491450.CrossRefGoogle ScholarPubMed
Walmsey, RS, Anthony, A, Sim, R, Pounder, RE & Wakefield, AJ (1998) Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues. J Clin Patholol 51, 657661.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, 215223.Google Scholar
Woywodt, A, Ludwig, D, Neustock, P, Kruse, A, Schwarting, K, Jantschek, G, Kirchner, H & Stange, EF (1999) Mucosal cytokine expression, cellular markers and adhesion molecules in inflammatory bowel disease. Eur J Gastroenterol Hepatol 11, 267276.Google Scholar
Yamaguchi, Y, Nagase, T, Makita, R, Fukuhara, S, Tomita, T, Tominaga, T, Kurihara, H & Ouchi, Y (2002) Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol 169, 25162523.CrossRefGoogle Scholar
Zhao, C, Wang, I & Lehrer, RI (1996) Widespread expression of beta defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396, 319325.Google Scholar
Zoetendal, EG, von Wright, A, Vilpponen-Salmela, T, Ben-Amor, K, Akkermans, AD, de Vos, WM (2002) Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distrubuted along the colon and differ from the community recovered from feces. Appl Environ Microbiol 68, 34013407.Google Scholar