Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1-/-;Nod2-/- Mice

被引：109

作者：

Natividad, Jane M. M. ^{[1
]}

Petit, Valerie ^{[2
]}

Huang, Xianxi ^{[1
]}

de Palma, Giada ^{[3
]}

Jury, Jennifer ^{[1
]}

Sanz, Yolanda ^{[3
]}

Philpott, Dana ^{[4
]}

Rodenas, Clara L. Garcia ^{[2
]}

McCoy, Kathy D. ^{[1
]}

Verdu, Elena F. ^{[1
]}

机构：

[1] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Hamilton, ON L8N 3Z5, Canada

[2] Nestle Res Ctr, CH-1000 Lausanne, Switzerland

[3] Spanish Natl Res Council IATA CSIC, Inst Agrochem & Food Technol, Valencia, Spain

[4] Univ Toronto, Dept Immunol, Toronto, ON, Canada

来源：

INFLAMMATORY BOWEL DISEASES | 2012年 / 18卷 / 08期

关键词：

intestinal barrier function; RegIII-; intestinal microbiota; altered Schaedler flora; Bifidobacterium breve; NOD-LIKE RECEPTORS; CROHNS-DISEASE; INSERTION/DELETION POLYMORPHISM; LISTERIA-MONOCYTOGENES; ADAPTIVE IMMUNITY; GENETIC-BASIS; CELL FUNCTION; PERMEABILITY; INNATE; MICROBIOTA;

D O I：

10.1002/ibd.22848

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: The intestinal microbiota regulates key host functions. It is unknown whether modulation of the microbiota can affect a genetically determined host phenotype. Polymorphisms in the Nucleotide oligomerization domain (Nod)-like receptor family confer genetic risk for inflammatory bowel disease (IBD). We investigated whether the intestinal microbiota and the probiotic strain Bifidobacterium breve NCC2950 affect intestinal barrier function and responses to intestinal injury in Nod1-/-;Nod2-/- mice. Methods: Specific pathogen-free (SPF) Nod1-/-;Nod2-/- mice and mice gnotobiotically derived with altered Schaedler flora (ASF) biota were used. SPF Nod1+/-;Nod2+/-littermates (generated by crossing SPF Nod1-/-;Nod2-/- and germ-free C57BL/6 mice) and ASF Nod1+/-;Nod2+/- mice were used as controls. SPF mice were gavaged daily with 109-CFU B. breve for 14 days before colitis induction. Denaturing gradient gel electrophoresis (DGGE) and real-time polymerase chain reaction (PCR) were used to assess microbiota composition. Intestinal permeability was assessed by in vitro and in vivo techniques. Expressions of epithelial apical junction proteins, mucin, and antimicrobial proteins were assessed by quantitative reverse-transcription PCR (qRT-PCR) and immunofluorescence. Responses to intestinal injury were investigated using an acute experimental model of colitis. Results: Under SPF conditions, Nod1-/-;Nod2-/- mice had increased paracellular permeability, decreased E-cadherin, and lower colonic antimicrobial RegIII-? expression compared to Nod1+/-;Nod2+/- littermate controls. These changes were associated with increased susceptibility to colitis. ASF colonization or B. breve supplementation normalized RegIII-? expression and decreased susceptibility to dextran sodium sulfate (DSS) colitis in Nod1-/-;Nod2-/- mice. Conclusions: The intestinal microbiota influences colitis severity in Nod1-/-;Nod2-/- mice. The results suggest that colonization strategies with defined commensals or exogenous specific probiotic therapy may prevent intestinal inflammation in a genetically predisposed host. (Inflamm Bowel Dis 2012)

引用

页码：1434 / 1446

页数：13

共 60 条

[1]

Arnott IDR, 2000, SCAND J GASTROENTERO, V35, P1163

[2] Alterations in intestinal permeability [J].

Arrieta, M. C. ;

Bistritz, L. ;

Meddings, J. B. .

GUT, 2006, 55 (10) :1512-1520

[3] CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice [J].

Barreau, Frederick ;

Meinzer, Ulrich ;

Chareyre, Fabrice ;

Berrebi, Dominique ;

Niwa-Kawakita, Michiko ;

Dussaillant, Monique ;

Foligne, Benoit ;

Ollendorff, Vincent ;

Heyman, Martine ;

Bonacorsi, Stephane ;

Lesuffleur, Thecla ;

Sterkers, Ghislaine ;

Giovannini, Marco ;

Hugot, Jean-Pierre .

PLOS ONE, 2007, 2 (06)

[4] Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches [J].

Barreau, Frederick ;

Madre, Chrystele ;

Meinzer, Ulrich ;

Berrebi, Dominique ;

Dussaillant, Monique ;

Merlin, Francoise ;

Eckmann, Lars ;

Karin, Mickael ;

Sterkers, Ghislaine ;

Bonacorsi, Stephane ;

Lesuffleur, Thecla ;

Hugot, Jean-Pierre .

GUT, 2010, 59 (02) :207-217

[5] Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection [J].

Bercík, P ;

De Giorgio, R ;

Blennerhassett, P ;

Verdú, EF ;

Barbara, G ;

Collins, SM .

GASTROENTEROLOGY, 2002, 123 (04) :1205-1215

[6] Crohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan [J].

Bonen, DK ;

Ogura, Y ;

Nicolae, DL ;

Inohara, N ;

Saab, L ;

Tanabe, T ;

Chen, FF ;

Foster, SJ ;

Duerr, RH ;

Brant, SR ;

Cho, JH ;

Nuñez, G .

GASTROENTEROLOGY, 2003, 124 (01) :140-146

[7] The immunological and genetic basis of inflammatory bowel disease [J].

Bouma, G ;

Strober, W .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :521-533

[8] Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis [J].

Bouskra, Djahida ;

Brezillon, Christophe ;

Berard, Marion ;

Werts, Catherine ;

Varona, Rosa ;

Boneca, Ivo Gomperts ;

Eberl, Gerard .

NATURE, 2008, 456 (7221) :507-U34

[9]

BRADLEY PP, 1982, BLOOD, V60, P618

[10] MyD88-mediated signals induce the bactericidal lectin RegIIIγ and protect mice against intestinal Listeria monocytogenes infection [J].

Brandl, Katharina ;

Plitas, George ;

Schnabl, Bernd ;

DeMatteo, Ronald P. ;

Pamer, Eric G. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1891-1900

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