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Probiotics for Prevention and Treatment of Clostridium difficile Infection

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Updates on Clostridium difficile in Europe

Abstract

Probiotics have been claimed as a valuable tool to restore the balance in the intestinal microbiota following a dysbiosis caused by, among other factors, antibiotic therapy. This perturbed environment could favor the overgrowth of Clostridium difficile and, in fact, the occurrence of C. difficile-associated infections (CDI) is being increasing in recent years. In spite of the high number of probiotics able to in vitro inhibit the growth and/or toxicity of this pathogen, its application for treatment or prevention of CDI is still scarce since there are not enough well-defined clinical studies supporting efficacy. Only a few strains, such as Lactobacillus rhamnosus GG and Saccharomyces boulardii have been studied in more extent. The increasing knowledge about the probiotic mechanisms of action against C. difficile, some of them reviewed here, makes promising the application of these live biotherapeutic agents against CDI. Nevertheless, more effort must be paid to standardize the clinical studied conducted to evaluate probiotic products, in combination with antibiotics, in order to select the best candidate for C. difficile infections.

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References

  • Abt MC, McKenney PT, Pamer EG (2016) Clostridium difficile colitis: pathogenesis and host defense. Nat Rev Microbiol 14:609–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allen SJ, Wareham K, Wang D et al (2013) Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 382:1249–1257

    Article  PubMed  Google Scholar 

  • Ambalam P, Kondepudi KK, Balusupati P et al (2015) Prebiotic preferences of human lactobacilli strains in co-culture with bifidobacteria and antimicrobial activity against Clostridium difficile. J Appl Microbiol 119:1672–1682

    Article  CAS  PubMed  Google Scholar 

  • Andersen KK, Strokappe NM, Hultberg A et al (2016) Neutralization of Clostridium difficile toxin B mediated by engineered lactobacilli that produce single-domain antibodies. Infect Immun 84:395–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arruda PHE, Madson DM, Ramirez A et al (2016) Bacterial probiotics as an aid in the control of Clostridium difficile disease in neonatal pigs. Can Vet J 57:183–188

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arvola T, Laiho K, Torkkeli S et al (1999) Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study. Pediatrics 104:64

    Article  Google Scholar 

  • Auclair J, Frappier M, Millette M (2015) Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+): characterization, manufacture, mechanisms of action, and quality control of a specific probiotic combination for primary prevention of Clostridium difficile infection. Clin Infect Dis 60:S135–S143

    Article  PubMed  Google Scholar 

  • Banerjee P, Merkel GJ, Bhunia AK (2009) Lactobacillus delbrueckii ssp. bulgaricus B-30892 can inhibit cytotoxic effects and adhesion of pathogenic Clostridium difficile to Caco-2 cells. Gut Pathog 1:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barreau F, Hugot JP (2014) Intestinal barrier dysfunction triggered by invasive bacteria. Curr Opin Microbiol 17:91–98

    Article  CAS  PubMed  Google Scholar 

  • Best EL, Freeman J, Wilcox MH (2012) Models for the study of Clostridium difficile infection. Gut Microbes 3:145–167

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolla PA, Carasi P, Serradell MA et al (2013) Kefir-isolated Lactococcus lactis subsp. lactis inhibits the cytotoxic effect of Clostridium difficile in vitro. J Dairy Res 80:96–102

    Article  CAS  PubMed  Google Scholar 

  • Boonma P, Spinler JK, Venable SF et al (2014) Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells. BMC Microbiol 14:177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Can M, Besirbellioglu BA, Avci IY et al (2006) Prophylactic Saccharomyces boulardii in the prevention of antibiotic associated diarrhea: a prospective study. Med Sci Monit 12:19–22

    Google Scholar 

  • Carasi P, Trejo FM, Pérez PF et al (2012) Surface proteins from Lactobacillus kefir antagonize in vitro cytotoxic effect of Clostridium difficile toxins. Anaerobe 18:135–142

    Article  CAS  PubMed  Google Scholar 

  • Carter GP, Rood JI, Lyras D (2012) The role of toxin A and toxin B in the virulence of Clostridium difficile. Trends Microbiol 20:21–29

    Article  CAS  PubMed  Google Scholar 

  • Castagliuolo I, Lamont JT, Nikulasson ST (1996) Saccharomyces boulardii protease inhibits Clostridium difficile Toxin A effects in the rat ileum. Infect Immun 64:5225–5232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Castagliuolo I, Rieger MF, Valenick L et al (1999) Saccharomyces boulardii protease inhibits the effect of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 67:302–307

    CAS  PubMed  PubMed Central  Google Scholar 

  • Collado MC, Gueimonde M, Hernández M et al (2005) Adhesion of selected Bifidobacterium strains to human intestinal mucus and its role in enteropathogen exclusion. J Food Protect 68:2672–2678

    Article  Google Scholar 

  • Corr SC, Li Y, Riedel CU et al (2007) Bacteriocin production as a mechanism for the anti-infective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A 104:7617–7621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cremonini F, Caro S, Nista EC et al (2002) Meta-analysis: the effects of probiotic administration on antibiotic associated diarrhoea. Aliment Pharmacol Ther 16:1461

    Article  CAS  PubMed  Google Scholar 

  • D’Souza AL, Rajkumar C, Cooke J et al (2002) Probiotics in the prevention of antibiotic associated diarrhoea: meta-analysis. Br Med J 324:1361

    Article  Google Scholar 

  • Dicks LMT, Botha M, Loos B et al (2015) Adhesion of Lactobacillus reuteri strain Lr1 to equine epithelial cells and competitive exclusion of Clostridium difficile from the gastro-intestinal tract of horses. Ann Microbiol 65:1087–1096

    Article  CAS  Google Scholar 

  • Dietrich CG, Kottmann T, Alavi M (2014) Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea. World J Gastroenterol 20:15837–15844

    Article  PubMed  PubMed Central  Google Scholar 

  • Donaldson GP, Lee SM, Mazmanian SK (2016) Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 14:20–32

    Article  CAS  PubMed  Google Scholar 

  • Ferreira CL, Grześkowiak Ł, Collado MC et al (2011) In vitro evaluation of Lactobacillus gasseri strains of infant origin on adhesion and aggregation of specific pathogens. J Food Prot 74:1482–1487

    Article  PubMed  Google Scholar 

  • Forssten SD, Röytió H, Hibberd AA et al (2015) The effect of polydextrose and probiotic lactobacilli in a Clostridium difficile-infected human colonic model. Microb Ecol Health Dis 26:27988

    PubMed  Google Scholar 

  • Fredua-Agyeman M, Stapleton P, Basit AW et al (2017) In vitro inhibition of Clostridium difficile by commercial probiotics: a microcalorimetric study. Int J Pharm 517:96–103

    Article  CAS  PubMed  Google Scholar 

  • Gagnon M, Zihler Berner A, Chervet N et al (2013) Comparison of the Caco-2, HT29 and the mucus-secreting HT29-MTX intestinal cell models to investigate Salmonella adhesion and invasion. J Microbiol Methods 94:274–279

    Article  CAS  PubMed  Google Scholar 

  • Gao XW, Mubasher M, Fang CY et al (2010) Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adults patients. Am J Gastroenterol 105:1636–1641

    Article  PubMed  Google Scholar 

  • Gareau MG, Sherman PM, Walker WA (2010) Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroentol Hepatol 7:503–514

    Article  Google Scholar 

  • Gerding DN, JohnsonS RM et al (2014) Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance. Gut Microb 5:15–27

    Article  Google Scholar 

  • Goldenberg JZ, Ma SSY, Saxton JD et al (2013) Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 5:CD006095

    Google Scholar 

  • Goldenberg JZ, Lytvyn L, Steurich J et al (2015) Probiotics for prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 12:CD004827

    Google Scholar 

  • Golić N, Veljović K, Popović N et al (2017) In vitro and in vivo antagonistic activity of new probiotic culture against Clostridium difficile and Clostridium perfringens. BMC Microbiol 17:108

    Article  PubMed  PubMed Central  Google Scholar 

  • Hempel S, Newberry SJ, Maher AR et al (2012) Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307:1959–1969

    Article  CAS  PubMed  Google Scholar 

  • Hickson M (2011) Probiotics in the prevention of antibiotic-associated diarrhea and Clostridium difficile infection. Ther Adv Gastroenterol 4:185–197

    Article  CAS  Google Scholar 

  • Hill C, Guarner F, Reid G et al (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514

    Article  PubMed  Google Scholar 

  • Hopkins MJ, Macfarlane GT (2003) Nondigestible oligosaccharides enhance bacterial colonization resistance against Clostridium difficile in vitro. Appl Environ Microbiol 69:1920–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussack G, Tanha J (2016) An update on antibody-based immunotherapies for Clostridium difficile infection. Clin Exp Gastroenterol 9:209–224

    Article  PubMed  PubMed Central  Google Scholar 

  • Hutton ML, Mackin KE, Chakravorty A et al (2014) Small animal models for the study of Clostridium difficile disease pathogenesis. FEMS Microbiol Lett 352:140–149

    Article  CAS  PubMed  Google Scholar 

  • Jangi S, Lamont JT (2010) Asyntomatic colonization by Clostridium difficile in infants: implications for disease in later life. J Pediatr Gastroenterol Nutr 51:2–7

    Article  PubMed  Google Scholar 

  • Johnston B, Supina A, Ospina M et al (2007) Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 18:CD004827

    Google Scholar 

  • Kachrimanidou M, Sarmourli T, Skoura L et al (2016) Clostridium difficile infection: new insights into therapeutic options. Crit Rev Microbiol 42:773–779

    PubMed  Google Scholar 

  • Kociolek LK, Gerding DN (2016) Breakthroughs in the treatment and prevention of Clostridium difficile infection. Nat Rev Gastroenterol Heptol 13:150–160

    Article  CAS  Google Scholar 

  • Kolling GL, Wu M, Warren CA et al (2012) Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro toxin A production. Gut Microb 3:523–529

    Article  Google Scholar 

  • Kondepudi KK, Ambalam P, Karagin PH et al (2014) A novel multi-strain probiotic and synbiotic supplement for prevention of Clostridium difficile infection in a murine model. Microbiol Immunol 58:552–558

    Article  CAS  PubMed  Google Scholar 

  • Koon HW, Su B, Xu C et al (2016) Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters. Am J Physiol Gastroenterol Liver Physiol 311:G610–G623

    Article  Google Scholar 

  • Kotowska M, Albrecht P, Szajewska H (2005) Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea in children: a randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther 21:583–590

    Article  CAS  PubMed  Google Scholar 

  • Lau CSM, Chamberlaim RS (2016) Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Int J Gen Med 9:27–37

    PubMed  PubMed Central  Google Scholar 

  • Lawley TD, Walker AW (2013) Intestinal colonization resistance. Immunology 138:1–11

    Article  CAS  PubMed  Google Scholar 

  • Le Lay C, Fernandez B, Hammami R et al (2015) On Lactococcus lactis UL719 competitivity and nisin (Nisaplin®) capacity to inhibit Clostridium difficile in a model of human colon. Front Microbiol 6:1020

    PubMed  PubMed Central  Google Scholar 

  • Leal JR, Heitman SJ, Conly JM et al (2016) Cost-effectiveness analysis of the use of probiotics for the prevention of Clostridium difficile-associated diarrhea in a provincial health care system. Infect Cont Hosp Epidemiol 37:1079–1086

    Article  Google Scholar 

  • Lee JS, Chung MJ, Seo JG (2013) In vitro evaluation of antimicrobial activity of lactic acid bacteria against Clostridium difficile. Toxicol Res 29:99–106

    Article  PubMed  PubMed Central  Google Scholar 

  • Leffler DA, Lamont JT (2015) Clostridium difficile infection. N Engl J Med 372:1539–1548

    Article  CAS  PubMed  Google Scholar 

  • Mansour NM, Elkhatib WF, Aboshnad KM et al (2017) Inhibition of Clostridium difficile in mice using a mixture of potential probiotic strains Enterococcus faecalis NM815, E. faecalis NM915, and E. faecium NM1015: novel candidates to control C. difficile infection (CDI). Probiotics Antimicrob Prot. https://doi.org/10.1007/s12602-017-9285-7. [E-pub ahead of print]

  • Martin J, Wilcox M (2016) New and emerging therapies for Clostridium difficile infection. Curr Opin Infect Dis 29:546–554

    Article  CAS  PubMed  Google Scholar 

  • Mathur H, Rea MC, Cotter PD et al (2014) The potential for emerging therapeutic options for Clostridium difficile infection. Gut Microb 5:696–710

    Article  Google Scholar 

  • Maziade PJ, Pereira P, Goldstein EJC (2015) A decade of experience in primary prevention of Clostridium difficile infection at a community hospital using the probiotic combination Lactobacillus acidophilus CL1285, Lactobacilus casei LBC80R, and Lactobacillus rhamnosus CRL2 (Bio-K+). Clin Infect Dis 60(Suppl 2):S144–S147

    Article  CAS  PubMed  Google Scholar 

  • McFarland LV (2006) Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 101:812–822

    Article  PubMed  Google Scholar 

  • McFarland LV (2015) Probiotics for the primary and secondary prevention of C. difficile infections. A meta-analysis and systematic review. Antibiotics 4:160–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McFarland LV (2016) Therapies on the horizon for Clostridium difficile infections. Expert Opin Investig Drugs 25:541–555

    Article  CAS  PubMed  Google Scholar 

  • McFarland LV, Surawicz CM, Greenberg RN et al (1994) A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. J Am Med Assoc 271:1913

    Article  CAS  Google Scholar 

  • Moura I, Spigaglia P, Barbanti F et al (2013) Analysis of metronidazole susceptibility in different Clostridium difficile PCR ribotypes. J Antimicrob Chemother 68:362–365

    Article  CAS  PubMed  Google Scholar 

  • Na X, Kelly C (2011) Probiotics in Clostridium difficile infection. J Clin Gastroenterol 45:S154–S158

    Article  PubMed  PubMed Central  Google Scholar 

  • Ng SC, Hart AL, Kamm MA et al (2009) Mechanisms of action of probiotics: recent advances. Inflamm Bowel Dis 15:300–310

    Article  CAS  PubMed  Google Scholar 

  • O’Horo JC, Jindai K, Kunzer B et al (2014) Treatment of recurrent Clostridium difficile infection: a systematic review. Infection 42:43–59

    Article  PubMed  CAS  Google Scholar 

  • Ofosu A (2016) Clostridium difficile infection: a review of current and emerging therapies. Ann Gastroenterol 29:147–154

    Article  PubMed  PubMed Central  Google Scholar 

  • Ollech JE, Shen NT, Crawford CV et al (2016) Use of probiotics in prevention and treatment of patients with Clostridium difficile infection. Best Pract Res Clin Gastroenterol 30:111–118

    Article  CAS  PubMed  Google Scholar 

  • Orrell KE, Zhanga Z, Sugiman-Marangosa SN et al (2017) Clostridium difficile toxins A and B: receptors, pores, and translocation into cells. Crit Rev Biochem Mol Biol 52:461–473

    Article  CAS  PubMed  Google Scholar 

  • Ozaki E, Kato H, Kita H et al (2004) Clostridium difficile colonization in healthy adults: transient colonization and correlation with enterococal colonization. J Med Microbiol 53:167–172

    Article  PubMed  Google Scholar 

  • Padua D, Pothoulakis C (2016) Novel approaches to treating Clostridium difficile-associated colitis. Expert Opin Investig Drugs 10:193–204

    CAS  Google Scholar 

  • Parkes GC, Sanderson JD, Whelan K (2009) The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea. Lancet Infect Dis 9:237–244

    Article  PubMed  Google Scholar 

  • Rätsep M, Kõljalg S, Sepp E et al (2017) A combination of the probiotic and prebiotic product can prevent the germination of Clostridium difficile spores and infection. Anaerobe 47:94–103

    Article  PubMed  CAS  Google Scholar 

  • Reid G, Younes JA, Van der Mei HC et al (2011) Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol 9:27–38

    Article  CAS  PubMed  Google Scholar 

  • Ripert G, Racedo SM, Elie AM et al (2016) Secreted compounds of the probiotic Bacillus clausii strain O/C inhibit the cytotoxic effects induced by Clostridium difficile and Bacillus cereus toxins. Antimicrob Agents Chemother 60:3445–3454

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodriguez C, Taminiau B, Van Broeck J et al (2016) Clostridium difficile in food and animals: a comprehensive review. Adv Exp Med Biol 4:65–92

    Article  Google Scholar 

  • Ruas-Madiedo P, Gueimonde M, Margolles A et al (2006) Exopolysaccharides produced by probiotic strains modify the adhesion of probiotics and enteropathogens to human intestinal mucus. J Food Prot 69:2011–2015

    Article  CAS  PubMed  Google Scholar 

  • Ruas-Madiedo P, Medrano M, Salazar N et al (2010) Exopolysaccharides produced by Lactobacillus and Bifidobacterium strains abrogate in vitro the cytotoxic effect of bacterial toxins on eukaryotic cells. J Appl Microbiol 109:2079–2086

    Article  CAS  PubMed  Google Scholar 

  • Rupnik M, Wilcox MH, Gerding DN (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 7:526–536

    Article  CAS  PubMed  Google Scholar 

  • Sampalis J, Psaradellis E, Ranpakakis E (2010) Efficacy of BIO K+ CL1285 in the reduction of antibiotic associated diarrhea- a placebo controlled double blind randomized, multi-centre study. Arch Med Sci 6:56–64

    PubMed  PubMed Central  Google Scholar 

  • Sazawal S, Hiremath G, Dhingra U et al (2006) Efficacy of probiotics in prevention of acute diarrhoea. A meta-analysis of masked, randomized, placebo-controlled trials. Lancet Infect Dis 6:374–382

    Article  PubMed  Google Scholar 

  • Schoster A, Kokotovic B, Permin A (2013) In vitro inhibition of Clostridium difficile and Clostridium perfringens by commercial probiotic strains. Anaerobe 20:36–41

    Article  CAS  PubMed  Google Scholar 

  • Shen NT, Maw A, Tmanova LL et al (2017) Timely use of probiotics in hospitalized adults prevents Clostridium difficile infection: a systematic review with meta-regression analysis. Gastroenterology 52:1889–1900

    Article  Google Scholar 

  • Sinclair A, Xie X, Saab L et al (2016) Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and bayesian hierarchical meta-analysis. CMAJ Open 4:E706–E718

    Article  PubMed  PubMed Central  Google Scholar 

  • Spinler JK, Brown A, Ross CL et al (2016) Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease. Anaerobe 40:54–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Starn ES, Hampe H, Cline T (2016) The cost-efficiency and care effectiveness of probiotic administration with antibiotics to prevent hospital-acquired Clostridium difficile infection. Qual Manag Health Care 25:238–243

    Article  PubMed  Google Scholar 

  • Stier H, Bischoff SC (2016) Influence of Saccharomyces boulardii CNCM I-745 on the gut-associated immune system. Clin Exp Gastroenterol 9:269–279

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun X, Wang H, Zhang Y et al (2011) Mouse relapse model of Clostridium difficile infection. Infect Immun 79:2856–2864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surawicz CM, McFarland LV, Greenberg RN et al (2000) The search for a better treatment for recurrent Clostridium difficile disease: use of high dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 31:1012–1017

    Article  CAS  PubMed  Google Scholar 

  • Szajewska H, Skorka A, Dylag M (2007a) Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. AP&T 25:257–264

    CAS  Google Scholar 

  • Szajewska H, Skorka A, Ruszczynski M et al (2007b) Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children. AP&T 25:871–881

    CAS  Google Scholar 

  • Szajewska H, Canani RB, Guarino A et al (2016) Probiotics for the prevention of antibiotic-associated diarrhea in children. J Pediatr Gastroenterol Nutr 62:495–506

    Article  CAS  PubMed  Google Scholar 

  • Tasteyre A, Barc MC, Karjalainen T et al (2002) Inhibition of in vitro cell adherence of Clostridium difficile by Saccharomyce boulardii. Microb Pathog 32:219–225

    Article  CAS  PubMed  Google Scholar 

  • Tejero-Sariñena S, Barlow J, Costabile A et al (2013) Antipathogenic activity of probiotics against Salmonella Typhimurium and Clostridium difficile in anaerobic batch culture systems: is it due to synergies in probiotic mixtures or the specificity of single strains? Anaerobe 24:60–65

    Article  PubMed  CAS  Google Scholar 

  • Trejo FM, Minnaard J, Pereza PF et al (2006) Inhibition of Clostridium difficile growth and adhesion to enterocytes by Bifidobacterium supernatants. Anaerobe 12:186–193

    Article  CAS  PubMed  Google Scholar 

  • Trejo FM, Pérez PF, De Antoni GL (2010) Co-culture with potentially probiotic microorganisms antagonises virulence factors of Clostridium difficile in vitro. Antonie Van Leeuwenhoek 98:19–29

    Article  CAS  PubMed  Google Scholar 

  • Trejo FM, De Antoni GL, Pérez PF (2013) Protective effect of bifidobacteria in an experimental model of Clostridium difficile associated colitis. J Dairy Res 80:263–269

    Article  CAS  PubMed  Google Scholar 

  • Ünal CM, Steinert M (2016) Novel therapeutic strategies for Clostridium difficile infections. Expert Opin Investig Drugs 20:269–285

    Google Scholar 

  • Valdés L, Gueimonde M, Ruas-Madiedo P (2015) Monitoring in real time the cytotoxic effect of Clostridium difficile upon the intestinal epithelial cell line HT29. J Microbiol Method 119:66–73

    Article  CAS  Google Scholar 

  • Valdés-Varela L, Alonso-Guervos M, García-Suárez O et al (2016a) Selection of bifidobacteria and lactobacilli able to antagonise the cytotoxic effect of Clostridium difficile upon intestinal epithelial HT29 monolayer. Front Microbiol 7:577

    PubMed  PubMed Central  Google Scholar 

  • Valdés-Varela L, Hernández-Barranco AM, Ruas-Madiedo P et al (2016b) Effect of Bifidobacterium upon Clostridium difficile growth and toxicity when co-cultured in different prebiotic substrates. Front Microbiol 7:738

    PubMed  PubMed Central  Google Scholar 

  • Vanderhoof J, Whitney D, Antonson D et al (1999) Lactobacillus GG in the prevention of antibiotic associated diarrhea in children. J Pediatr 135:564–568

    Article  CAS  PubMed  Google Scholar 

  • Venema K, van den Abbeele P (2013) Experimental models of the gut microbiome. Best Pract Res Clin Gastroenterol 27:115–126

    Article  CAS  PubMed  Google Scholar 

  • Vernaya M, McAdam J, Hamptom MD (2017) Effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients: a systematic review. JBI Database Syst Rev Impl Rep 15:140–164

    Article  Google Scholar 

  • Voth DE, Ballard JD (2005) Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18:247–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodworth MH, Carpentieri C, Sitchenko KL et al (2017) Challenges in fecal donor selection and screening for fecal microbiota transplantation: a review. Gut Microb 8:225–237

    Article  Google Scholar 

  • Wullt M, Hagslatt ML, Odenholt I (2003) Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scand J Infect Dis 35:365–367

    Article  PubMed  Google Scholar 

  • Xi B, Yu N, Wang X et al (2008) The application of cell-based label-free technology in drug discovery. Biotechnol J 3:484–495

    Article  CAS  PubMed  Google Scholar 

  • Yakob L, Riley TV, Paterson DL et al (2015) Mechanisms of hypervirulent Clostridium difficile ribotype 027 displacement of endemic strains: an epidemiological model. Sci Rep 5:12666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young VB (2017) Old and new models for studying host-microbe interactions in health and disease: C. difficile as an example. Am J Physiol Gastrointest Liver Physiol 312:G623–G627

    Article  PubMed  Google Scholar 

  • Yu H, Chen K, Wu J et al (2015) Identification of toxemia in patients with Clostridium difficile infection. PLoS One 10:e0124235

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yun B, Oh S, Griffiths MW (2014) Lactobacillus acidophilus modulates the virulence of Clostridium difficile. J Dairy Sci 97:4745–4758

    Article  CAS  PubMed  Google Scholar 

  • Zivkovic M, Hidalgo-Cantabrana C, Kojic M et al (2015) Capability of exopolysaccharide-producing Lactobacillus paraplantarum BGCG11 and its non-producing isogenic strain NB1, to counteract the effect of enteropathogens upon the epithelial cell line HT29-MTX. Food Res Int 74:199–207

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The funds supporting this research topic in our group are given by the Spanish Ministry of Economy and Competiveness (current project AGL2015-64901-R) partially co-funded by FEDER (European Union) grants.

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Valdés-Varela, L., Gueimonde, M., Ruas-Madiedo, P. (2018). Probiotics for Prevention and Treatment of Clostridium difficile Infection. In: Mastrantonio, P., Rupnik, M. (eds) Updates on Clostridium difficile in Europe. Advances in Experimental Medicine and Biology(), vol 1050. Springer, Cham. https://doi.org/10.1007/978-3-319-72799-8_10

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