All Title Author
Keywords Abstract

PLOS ONE  2012 

Lactobacillus reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction

DOI: 10.1371/journal.pone.0046399

Full-Text   Cite this paper   Add to My Lib


Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte- and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis.


[1]  Packey CD, Sartor RB (2009) Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr Opin Infect Dis 22: 292–301.
[2]  Atuma C, Strugala V, Allen A, Holm L (2001) The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol 280: G922–929.
[3]  Petersson J, Schreiber O, Hansson GC, Gendler SJ, Velcich A, et al. (2011) Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 300: G327–333.
[4]  Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, et al. (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A 105: 15064–15069.
[5]  Jager S, Stange EF, Wehkamp J (2010) Antimicrobial peptides in gastrointestinal inflammation. Int J Inflam 2010: 910283.
[6]  Marchiando AM, Graham WV, Turner JR (2010) Epithelial barriers in homeostasis and disease. Annu Rev Pathol 5: 119–144.
[7]  Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, et al. (2007) Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME journal 1: 403–418.
[8]  Dicksved J, Halfvarson J, Rosenquist M, J?rnerot G, Tysk C, et al. (2008) Molecular analysis of the gut microbiota of identical twins with Crohn's disease. ISME J 2: 716–727.
[9]  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.
[10]  Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, et al. (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 52: 237–242.
[11]  Willing B, Dicksved J, Halfvarson J, Andersson A, Lucio M, et al. (2010) A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139: 1844–1854.
[12]  Willing B, Halfvarson J, Dicksved J, Rosenquist M, J?rnerot G, et al. (2009) Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm Bowel Dis 15: 653–660.
[13]  Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, et al. (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104: 13780–13785.
[14]  Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, et al. (2006) Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55: 205–211.
[15]  Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59–65.
[16]  Tamboli CP, Neut C, Desreumaux P, Colombel JF (2004) Dysbiosis in inflammatory bowel disease. Gut 53: 1–4.
[17]  Schreiber O, Petersson J, Phillipson M, Perry M, Roos S, et al. (2009) Lactobacillus reuteri prevents colitis by reducing P-selectin-associated leukocyte- and platelet-endothelial cell interactions. Am J Physiol Gastrointest Liver Physiol 296: G534–542.
[18]  Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69: 238–249.
[19]  Benjamini Y, Hochberg Y (1995) Controling the false discovery rate: a practical and powerful approach to multiple testing. JR Stat Soc Series B Methodol 57: 289–300.
[20]  Lupp C, Robertson ML, Wickham ME, Sekirov I, Champion OL, et al. (2007) Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2: 204.
[21]  Lamine F, Eutamene H, Fioramonti J, Bueno L, Theodorou V (2004) Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats. Scand J Gastroenterol 39: 1250–1258.
[22]  Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, et al. (1998) Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 115: 1405–1413.
[23]  Ye J, Lee JW, Presley LL, Bent E, Wei B, et al. (2008) Bacteria and bacterial rRNA genes associated with the development of colitis in IL-10(?/?) mice. Inflamm Bowel Dis 14: 1041–1050.
[24]  McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G (2009) Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis 15: 100–113.
[25]  Mennigen R, Nolte K, Rijcken E, Utech M, Loeffler B, et al. (2009) Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 296: G1140–1149.
[26]  Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA (2003) Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut 52: 827–833.
[27]  Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA (1999) Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol 276: G941–950.


comments powered by Disqus

Contact Us


微信:OALib Journal