Effect of Probiotics on Intestinal Barrier Function in Mice with Inflammatory Bowel Disease_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Hongqi ¹ , YANG Jun ¹ , ZHOU Yukun ¹ , ZHANG Min ² , HANG Xiaomin ² ,  QIN Huanlong. ¹

1.Department of General Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China2.Institute of BioMedicine, Shanghai Jiao Tong University, Shanghai 200233, China;

Corresponding author：

QIN Huanlong., Email: hlqin@sjtu.edu.cn

Keywords：

Probiotic; Lactobacillus plantarum; Intestinal barrier; Tight junction protein

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ObjectiveTo investigate the effect of Lactobacillus plantarum (LP) on the intestinal barrier function under inflammation. MethodsInterleukin-10 knockout (IL-10－/－) mice were used as the model of inflammatory bowel disease. IL-10－/－ and wild type (WT) mice received the LP or Ringer solutions for 4 weeks. Colitis was assessed by histological score and clinical manifestation was observed. The gut paracellular permeability was measured by Ussing chamber. The concentrations of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected by the ELISA method. The expressions and distributions of tight junction proteins were determined by Western blot and immunofluorescence, respectively. ResultsCompared with the WT group, the diarrhea, rectal prolapse, and weight loss were obvious (P lt;0.01), the concentrations of TNF-α and IFN-γ significantly increased (P lt;0.01), the infiltration of numerous inflammatory cells, even transmural ulcers, and crypt abscess were observed, the ultrastructure of tight junction was damaged, the mannitol permeability significantly increased (P lt;0.001) and transepithelial resistance (TER) significantly decreased (P lt;0.001), and the expressions of tight junction proteins (ZO-1, occludin, and claudin-1) significantly decreased (P lt;0.01) in the IL-10－/－ group. Compared with the IL-10－/－ group, the clinical and pathological manifestations of colitis significantly improved (P lt;0.01), the ultrastructural damage of tight junction was prevented, the mannitol permeability significantly decreased (P lt;0.001) and the TER significantly increased (P lt;0.001), the concentrations of TNF-α and IFN-γ significantly decreased (P lt;0.01), and the expressions of tight junction proteins (ZO-1, occludin, and claudin-1) significantly increased (P lt;0.01) in the IL-10－/－+LP group. ConclusionTreatment with LP ameliorates colonic epithelial barrier dysfunction by promoting the expressions of tight junctional proteins in IL-10－/－ mice.

Citation： CHEN Hongqi,YANG Jun,ZHOU Yukun,ZHANG Min,HANG Xiaomin,QIN Huanlong.. Effect of Probiotics on Intestinal Barrier Function in Mice with Inflammatory Bowel Disease. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(12): 1242-1247. doi: Copy

1.	Guarner F, Malagelada JR. Gut flora in health and disease [J]. Lancet, 2003, 361(9356): 512519.
2.	Sartor RB. Microbial influences in inflammatory bowel diseases [J]. Gastroenterology, 2008, 134(2): 577594.
3.	Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics [J]. Gastroenterology, 2001, 120(3): 622635.
4.	Hedin C, Whelan K, Lindsay JO. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials [J]. Proc Nutr Soc, 2007, 66(3): 307315.
5.	Berg DJ, Davidson N, Kühn R, et al. Enterocolitis and colon cancer in interleukin10deficient mice are associated with aberrant cytokine production and CD4(+) TH1like responses [J]. J Clin Invest, 1996, 98(4): 10101020.
6.	Zeissig S, Bürgel N, Günzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease [J]. Gut, 2007, 56(1): 6172.
7.	Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function [J]. Gastroenterology, 2001, 121(3): 580591.
8.	Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation [J]. Immunol Res, 2004, 29(13): 5568.
9.	Munkholm P, Langholz E, Hollander D, et al. Intestinal permeability in patients with Crohn’s disease and ulcerative colitis and their first degree relatives [J]. Gut, 1994, 35(1): 6872.
10.	Peeters M, Geypens B, Claus D, et al. Clustering of increased small intestinal permeability in families with Crohn’s disease[J]. Gastroenterology， 1997, 113(3): 802807.
11.	Prasad S, Mingrino R, Kaukinen K, et al. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells [J]. Lab Invest, 2005, 85(9): 11391162.
12.	DarfeuilleMichaud A, Boudeau J, Bulois P, et al. High prevalence of adherentinvasive Escherichia coli associated with ileal mucosa in Crohn’s disease [J]. Gastroenterology, 2004, 127(2): 412421.
13.	Martin HM, Campbell BJ, Hart CA, et al. Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer [J]. Gastroenterology, 2004, 127(1): 8093.
14.	Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases [J]. Inflamm Bowel Dis, 2008, 14(11): 15851596.
15.	JohnsonHenry KC, Donato KA, ShenTu G, et al. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157: H7induced changes in epithelial barrier function [J]. Infect Immun, 2008, 76(4): 13401348.
16.	RestaLenert S, Barrett KE. Probiotics and commensals reverse TNFalpha and IFNgammainduced dysfunction in human intestinal epithelial cells [J]. Gastroenterology, 2006, 130(3): 731746.
17.	RestaLenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) [J]. Gut, 2003, 52(7): 988997.
18.	Qin HL, Zhang ZW, Hang XM, et al. L. plantarum prevents enteroinvasive Escherichia coliinduced tight junction proteins changes in intestinal epithelial cells [J]. BMC Microbiol, 2009, 9: 6371.

1. Guarner F, Malagelada JR. Gut flora in health and disease [J]. Lancet, 2003, 361(9356): 512519.
2. Sartor RB. Microbial influences in inflammatory bowel diseases [J]. Gastroenterology, 2008, 134(2): 577594.
3. Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics [J]. Gastroenterology, 2001, 120(3): 622635.
4. Hedin C, Whelan K, Lindsay JO. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials [J]. Proc Nutr Soc, 2007, 66(3): 307315.
5. Berg DJ, Davidson N, Kühn R, et al. Enterocolitis and colon cancer in interleukin10deficient mice are associated with aberrant cytokine production and CD4(+) TH1like responses [J]. J Clin Invest, 1996, 98(4): 10101020.
6. Zeissig S, Bürgel N, Günzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease [J]. Gut, 2007, 56(1): 6172.
7. Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function [J]. Gastroenterology, 2001, 121(3): 580591.
8. Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation [J]. Immunol Res, 2004, 29(13): 5568.
9. Munkholm P, Langholz E, Hollander D, et al. Intestinal permeability in patients with Crohn’s disease and ulcerative colitis and their first degree relatives [J]. Gut, 1994, 35(1): 6872.
10. Peeters M, Geypens B, Claus D, et al. Clustering of increased small intestinal permeability in families with Crohn’s disease[J]. Gastroenterology， 1997, 113(3): 802807.
11. Prasad S, Mingrino R, Kaukinen K, et al. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells [J]. Lab Invest, 2005, 85(9): 11391162.
12. DarfeuilleMichaud A, Boudeau J, Bulois P, et al. High prevalence of adherentinvasive Escherichia coli associated with ileal mucosa in Crohn’s disease [J]. Gastroenterology, 2004, 127(2): 412421.
13. Martin HM, Campbell BJ, Hart CA, et al. Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer [J]. Gastroenterology, 2004, 127(1): 8093.
14. Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases [J]. Inflamm Bowel Dis, 2008, 14(11): 15851596.
15. JohnsonHenry KC, Donato KA, ShenTu G, et al. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157: H7induced changes in epithelial barrier function [J]. Infect Immun, 2008, 76(4): 13401348.
16. RestaLenert S, Barrett KE. Probiotics and commensals reverse TNFalpha and IFNgammainduced dysfunction in human intestinal epithelial cells [J]. Gastroenterology, 2006, 130(3): 731746.
17. RestaLenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) [J]. Gut, 2003, 52(7): 988997.
18. Qin HL, Zhang ZW, Hang XM, et al. L. plantarum prevents enteroinvasive Escherichia coliinduced tight junction proteins changes in intestinal epithelial cells [J]. BMC Microbiol, 2009, 9: 6371.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Probiotics on Intestinal Barrier Function in Mice with Inflammatory Bowel Disease

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