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Published in: Digestive Diseases and Sciences 3/2012

01-03-2012 | Original Article

Effects of a Lactobacillus reuteri BR11 Mutant Deficient in the Cystine-Transport System in a Rat Model of Inflammatory Bowel Disease

Authors: Haydn L. Atkins, Mark S. Geier, Luca D. Prisciandaro, Ashok K. Pattanaik, Rebecca E. A. Forder, Mark S. Turner, Gordon S. Howarth

Published in: Digestive Diseases and Sciences | Issue 3/2012

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Abstract

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract associated with altered composition of the gut microbiota. Lactobacillus reuteri BR11 (BR11) has recently been reported to reduce the severity of experimental IBD because of its probiotic properties possibly attributed to a mechanism of thiol production via its unique cysteine/cystine-transport system.

Aim

We compared BR11 and a BR11 mutant deficient in the cystine-uptake system (PNG201), for their capacity to reduce the severity of experimental colitis.

Methods

Male Sprague–Dawley rats (n = 8 per group) were gavaged (1 ml/day) with skim milk, BR11 or PNG201 (1 × 109 CFU/ml) for 12 days. Rats consumed either water or 2% dextran sulfate sodium in drinking water from days 6 to 12 to induce colitis. Metabolism data, disease activity index, intestinal mucin profile, and histological analyses were assessed and compared by ANOVA.

Results

Assessed histologically, DSS administration resulted in significant colonic deterioration, including loss of crypt area and increased damage severity. BR11 administration only partially alleviated the DSS effects, with a minor improvement in crypt area (P < 0.05). Administration of the PNG201 mutant strain to colitic animals failed to achieve significance (P > 0.05) against the DSS control for any of the end-points. However, the mutant strain induced significantly greater (P < 0.05) histological severity compared with BR11-treated colitic animals, indicative of possible exacerbation of colitis.

Conclusions

The cystine-uptake system only minimally affects the biological effects of BR11, as evidenced by histological and macroscopic colitic changes.
Literature
1.
go back to reference Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12:S3–S9.PubMedCrossRef Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12:S3–S9.PubMedCrossRef
2.
go back to reference Amit-Romach E, Uni Z, Reifen R. Therapeutic potential of two probiotics in inflammatory bowel disease as observed in the trinitrobenzene sulfonic acid model of colitis. Dis Colon Rectum. 2008;51:1828–1836.PubMedCrossRef Amit-Romach E, Uni Z, Reifen R. Therapeutic potential of two probiotics in inflammatory bowel disease as observed in the trinitrobenzene sulfonic acid model of colitis. Dis Colon Rectum. 2008;51:1828–1836.PubMedCrossRef
3.
go back to reference Shanahan F. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv Drug Deliv Rev. 2004;56:809–818.PubMedCrossRef Shanahan F. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv Drug Deliv Rev. 2004;56:809–818.PubMedCrossRef
4.
go back to reference Boudeau J, Glasser AL, Julien S, Colombel JF, Darfeuille-Michaud A. Inhibitory effect of probiotic escherichia coli strain nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive e-coli strains isolated from patients with crohn’s disease. Aliment Pharmacol Ther. 2003;18:45–56.PubMedCrossRef Boudeau J, Glasser AL, Julien S, Colombel JF, Darfeuille-Michaud A. Inhibitory effect of probiotic escherichia coli strain nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive e-coli strains isolated from patients with crohn’s disease. Aliment Pharmacol Ther. 2003;18:45–56.PubMedCrossRef
5.
go back to reference Chapman TM, Plosker GL, Figgitt DP. Vsl #3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs. 2006;66:1371–1387.PubMedCrossRef Chapman TM, Plosker GL, Figgitt DP. Vsl #3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs. 2006;66:1371–1387.PubMedCrossRef
6.
go back to reference Peran L, Sierra S, Comalada M, et al. A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis. Br J Nutr. 2007;97:96–103.PubMedCrossRef Peran L, Sierra S, Comalada M, et al. A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis. Br J Nutr. 2007;97:96–103.PubMedCrossRef
7.
go back to reference Seksik P, Dray X, Sokol H, Marteau P. Is there any place for alimentary probiotics, prebiotics or synbiotics, for patients with inflammatory bowel disease? Mol Nutr Food Res. 2008;52:906–912.PubMedCrossRef Seksik P, Dray X, Sokol H, Marteau P. Is there any place for alimentary probiotics, prebiotics or synbiotics, for patients with inflammatory bowel disease? Mol Nutr Food Res. 2008;52:906–912.PubMedCrossRef
8.
go back to reference Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: implications for therapeutic applications in inflammatory bowel diseases. Inflam Bowel Dis. 2008;14:1585–1596.CrossRef Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: implications for therapeutic applications in inflammatory bowel diseases. Inflam Bowel Dis. 2008;14:1585–1596.CrossRef
9.
go back to reference Geier MS, Butler RN, Howarth GS. Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics. Int J Food Microbiol. 2007;115:1–11.PubMedCrossRef Geier MS, Butler RN, Howarth GS. Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics. Int J Food Microbiol. 2007;115:1–11.PubMedCrossRef
10.
go back to reference Mahida YR, Rolfe VE. Host-bacterial interactions in inflammatory bowel disease. Clin Sci. 2004;107:331–341.PubMedCrossRef Mahida YR, Rolfe VE. Host-bacterial interactions in inflammatory bowel disease. Clin Sci. 2004;107:331–341.PubMedCrossRef
11.
go back to reference Rioux KP, Madsen KL, Fedorak RN. The role of enteric microflora in inflammatory bowel disease: human, animal studies with probiotics, prebiotics. Gastroenterol Clin N Am. 2005;34:465–482.CrossRef Rioux KP, Madsen KL, Fedorak RN. The role of enteric microflora in inflammatory bowel disease: human, animal studies with probiotics, prebiotics. Gastroenterol Clin N Am. 2005;34:465–482.CrossRef
12.
go back to reference Amit-Romach E, Uni Z, Reifen R. Mulistep mechanism of probiotic bacterium, the effect on innate immune system. Mol Nutr Food Res. 2010;54:277–284.PubMedCrossRef Amit-Romach E, Uni Z, Reifen R. Mulistep mechanism of probiotic bacterium, the effect on innate immune system. Mol Nutr Food Res. 2010;54:277–284.PubMedCrossRef
13.
go back to reference Turner MS, Woodberry T, Hafner LM, Gliffard PM. The bspA locus of Lactobacillus fermentum BR11 encodes an l-cystine uptake system. J Bacteriol. 1999;181:2192–2198.PubMed Turner MS, Woodberry T, Hafner LM, Gliffard PM. The bspA locus of Lactobacillus fermentum BR11 encodes an l-cystine uptake system. J Bacteriol. 1999;181:2192–2198.PubMed
14.
go back to reference Geier MS, Butler RN, Giffard PM, Howarth GS. Lactobacillus fermentum BR11, a potential new probiotic, alleviates symptoms of colitis induced by dextran sulfate sodium (dss) in rats. Int J Food Microbiol. 2007;114:267–274.PubMedCrossRef Geier MS, Butler RN, Giffard PM, Howarth GS. Lactobacillus fermentum BR11, a potential new probiotic, alleviates symptoms of colitis induced by dextran sulfate sodium (dss) in rats. Int J Food Microbiol. 2007;114:267–274.PubMedCrossRef
15.
go back to reference Lo R, Turner MS, Barry DG, Sreekumar R, Walsh TP, Gliffard PM. Cystathionine gamma-lyase is a component of cystine-mediated oxidative defense in Lactobacillus reuteri BR11. J Bacteriol. 2009;191:1827–1837.PubMedCrossRef Lo R, Turner MS, Barry DG, Sreekumar R, Walsh TP, Gliffard PM. Cystathionine gamma-lyase is a component of cystine-mediated oxidative defense in Lactobacillus reuteri BR11. J Bacteriol. 2009;191:1827–1837.PubMedCrossRef
16.
go back to reference Turner MS, Timms P, Hafner LM, Gliffard PM. Identification and characterization of a basic cell surface-located protein from Lactobacillus fermentum BR11. J Bacteriol. 1997;179:3310–3316.PubMed Turner MS, Timms P, Hafner LM, Gliffard PM. Identification and characterization of a basic cell surface-located protein from Lactobacillus fermentum BR11. J Bacteriol. 1997;179:3310–3316.PubMed
17.
go back to reference Javed S, Howard A, Hirst B. Protection of intestinal cells against reactive oxygen species (ros) by amino acids. Mutagenesis. 2009;24:38. Javed S, Howard A, Hirst B. Protection of intestinal cells against reactive oxygen species (ros) by amino acids. Mutagenesis. 2009;24:38.
18.
go back to reference Damiani CR, Benetton CAF, Stoffel C, et al. Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol. 2007;22:1846–1851.PubMedCrossRef Damiani CR, Benetton CAF, Stoffel C, et al. Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol. 2007;22:1846–1851.PubMedCrossRef
19.
go back to reference Sengul N, Isik S, Aslim B, Ucar G, Demirbag AE. The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis. Dig Dis Sci. 2011;56:707–714.PubMedCrossRef Sengul N, Isik S, Aslim B, Ucar G, Demirbag AE. The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis. Dig Dis Sci. 2011;56:707–714.PubMedCrossRef
20.
go back to reference Hung J, Turner MS, Walsh T, Giffard PM. Bspa (CyuC) in Lactobacillus reuteri BR11 is a highly expressed high-affinity l-cystine-binding protein. Curr Microbiol. 2005;50:33–37.PubMedCrossRef Hung J, Turner MS, Walsh T, Giffard PM. Bspa (CyuC) in Lactobacillus reuteri BR11 is a highly expressed high-affinity l-cystine-binding protein. Curr Microbiol. 2005;50:33–37.PubMedCrossRef
21.
go back to reference Hung J, Cooper D, Turner MS, Walsh T, Giffard PM. Cystine uptake prevents production of hydrogen peroxide by Lactobacillus fermentum BR11. FEMS Microbiol Lett. 2003;227:93–99.PubMedCrossRef Hung J, Cooper D, Turner MS, Walsh T, Giffard PM. Cystine uptake prevents production of hydrogen peroxide by Lactobacillus fermentum BR11. FEMS Microbiol Lett. 2003;227:93–99.PubMedCrossRef
22.
go back to reference Rush CM, Hafner LM, Timms P. Genetic-modification of a vaginal strain of lactobacillus fermentum and its maintenance within the reproductive-tract after intravaginal administration. J Med Microbiol. 1994;41:272–278.PubMedCrossRef Rush CM, Hafner LM, Timms P. Genetic-modification of a vaginal strain of lactobacillus fermentum and its maintenance within the reproductive-tract after intravaginal administration. J Med Microbiol. 1994;41:272–278.PubMedCrossRef
23.
go back to reference Tomas FM, Knowles SE, Owens PC, et al. Effects of full-length and truncated insulin-like growth factor-i on nitrogen-balance and muscle protein-metabolism in nitrogen-restricted rats. J Endocrinol. 1991;128:97–105.PubMedCrossRef Tomas FM, Knowles SE, Owens PC, et al. Effects of full-length and truncated insulin-like growth factor-i on nitrogen-balance and muscle protein-metabolism in nitrogen-restricted rats. J Endocrinol. 1991;128:97–105.PubMedCrossRef
24.
go back to reference Howarth GS, Xian CJ, Read LC. Predisposition to colonic dysplasia is unaffected by continuous administration of insulin-like growth factor-i for 20 weeks in a rat model of chronic inflammatory bowel disease. Growth Fact. 2000;18:119–133.CrossRef Howarth GS, Xian CJ, Read LC. Predisposition to colonic dysplasia is unaffected by continuous administration of insulin-like growth factor-i for 20 weeks in a rat model of chronic inflammatory bowel disease. Growth Fact. 2000;18:119–133.CrossRef
25.
go back to reference Howarth GS, Xian CJ, Read LC. Insulin-like growth factor-1 partially attenuates colonic damage in rats with experimental colitis induced by oral dextran sulphate sodium. Scand J Gastroenterol. 1998;33:180–190.PubMedCrossRef Howarth GS, Xian CJ, Read LC. Insulin-like growth factor-1 partially attenuates colonic damage in rats with experimental colitis induced by oral dextran sulphate sodium. Scand J Gastroenterol. 1998;33:180–190.PubMedCrossRef
26.
go back to reference Gaudio E, Taddei G, Vetuschi A, et al. Dextran sulfate sodium (dss) colitis in rats: clinical, structural, and ultrastructural aspects. Dig Dis Sci. 1999;44:1458–1475.PubMedCrossRef Gaudio E, Taddei G, Vetuschi A, et al. Dextran sulfate sodium (dss) colitis in rats: clinical, structural, and ultrastructural aspects. Dig Dis Sci. 1999;44:1458–1475.PubMedCrossRef
27.
go back to reference Howarth GS, Francis GL, Cool JC, Xu X, Byard RW, Read LC. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. J Nutr. 1996;126:2519–2530.PubMed Howarth GS, Francis GL, Cool JC, Xu X, Byard RW, Read LC. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. J Nutr. 1996;126:2519–2530.PubMed
28.
go back to reference Longman RJ, Poulson R, Corfield AP, Warren BF, Wright NA, Thomas MG. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. J Histochem Cytochem. 2006;54:1335–1348.PubMedCrossRef Longman RJ, Poulson R, Corfield AP, Warren BF, Wright NA, Thomas MG. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. J Histochem Cytochem. 2006;54:1335–1348.PubMedCrossRef
29.
go back to reference Corfield AP, Myerscough N, Bradfield N, et al. Colonic mucins in ulcerative colitis: evidence for loss of sulfation. Glycoconj J. 1996;13:809–822.PubMedCrossRef Corfield AP, Myerscough N, Bradfield N, et al. Colonic mucins in ulcerative colitis: evidence for loss of sulfation. Glycoconj J. 1996;13:809–822.PubMedCrossRef
30.
go back to reference Forder REA, Howarth GS, Tivey DR, Hughes RJ. Bacterial modulation of small intestinal goblet cells and mucin composition during early posthatch development of poultry. Poult Sci. 2007;86:2396–2403.PubMedCrossRef Forder REA, Howarth GS, Tivey DR, Hughes RJ. Bacterial modulation of small intestinal goblet cells and mucin composition during early posthatch development of poultry. Poult Sci. 2007;86:2396–2403.PubMedCrossRef
31.
go back to reference Yan YT, Kolachala V, Dalmasso G, et al. Temporal, spatial analysis of clinical, molecular parameters in dextran sodium sulfate induced colitis. Plos One. 2009;4:e6073.PubMedCrossRef Yan YT, Kolachala V, Dalmasso G, et al. Temporal, spatial analysis of clinical, molecular parameters in dextran sodium sulfate induced colitis. Plos One. 2009;4:e6073.PubMedCrossRef
32.
go back to reference Vetuschi A, Latella G, Sferra R, Caprilli R, Gaudio E. Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats. Dig Dis Sci. 2002;47:1447–1457.PubMedCrossRef Vetuschi A, Latella G, Sferra R, Caprilli R, Gaudio E. Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats. Dig Dis Sci. 2002;47:1447–1457.PubMedCrossRef
33.
go back to reference Shimizu T, Suzuki M, Fujimura J, et al. The relationship between the concentration of dextran sodium sulfate and the degree of induced experimental colitis in weanling rats. J Pediatr Gastroenterol Nutr. 2003;37:481–486.PubMedCrossRef Shimizu T, Suzuki M, Fujimura J, et al. The relationship between the concentration of dextran sodium sulfate and the degree of induced experimental colitis in weanling rats. J Pediatr Gastroenterol Nutr. 2003;37:481–486.PubMedCrossRef
34.
go back to reference Mauger CA, Butler RN, Geier MS, Tooley KL, Howarth GS. Probiotic effects on 5-fluorouracil-induced mucositis assessed by the sucrose breath test in rats. Dig Dis Sci. 2007;52:612–619. Mauger CA, Butler RN, Geier MS, Tooley KL, Howarth GS. Probiotic effects on 5-fluorouracil-induced mucositis assessed by the sucrose breath test in rats. Dig Dis Sci. 2007;52:612–619.
35.
go back to reference Geier MS, Butler RN, Giffard PM, Howarth GS. Prebiotic and synbiotic fructooligosaccharide administration fails to reduce the severity of experimental colitis in rats. Dis Colon Rectum. 2007;50:1061–1069.PubMedCrossRef Geier MS, Butler RN, Giffard PM, Howarth GS. Prebiotic and synbiotic fructooligosaccharide administration fails to reduce the severity of experimental colitis in rats. Dis Colon Rectum. 2007;50:1061–1069.PubMedCrossRef
Metadata
Title
Effects of a Lactobacillus reuteri BR11 Mutant Deficient in the Cystine-Transport System in a Rat Model of Inflammatory Bowel Disease
Authors
Haydn L. Atkins
Mark S. Geier
Luca D. Prisciandaro
Ashok K. Pattanaik
Rebecca E. A. Forder
Mark S. Turner
Gordon S. Howarth
Publication date
01-03-2012
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 3/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-011-1943-0

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