Probiotics in the Treatment of Inflammatory Bowel Disease

  • Stefano GuandaliniEmail author
  • Naire Sansotta
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1125)


While considerable progress has been made in the treatment of inflammatory bowel diseases (IBD), alternative options are constantly sought by adult patients as well as frustrated parents of young patients. These include dietary modifications, food supplements, and, more recently, probiotics.

Their potential use is based on the demonstrated role of the altered mucosal immune response to bacterial agents that eventually leads to the chronic intestinal inflammation that characterized IBD. In fact, probiotics might conceivably be beneficial due to multiple mechanisms: stimulation of anti-inflammatory cytokines, inhibition of inflammatory cytokines, strengthening of intestinal barrier, and antagonistic action on pathogens. Such mechanisms have been largely extensively investigated in animal models both in vitro and in vivo.

Despite such premise, a relatively scarce number of clinical trials are available, and of them only a handful in pediatric age. Overall, available evidence is very disappointing in the treatment of Crohn’s disease (CD), where no recommendation for probiotic use can be made. In ulcerative colitis (UC), on the other hand, there is clinical evidence of efficacy for some specific strains and especially for multi-strain preparations.

In summary, more data are needed very likely to yield a better understanding on what strains and in what doses should be used in different specific clinical settings.


Crohn’s disease IBD Inflammatory bowel disease Lactobacillus Probiotics Ulcerative colitis De Simone Formulation 


  1. Abraham BP, Quigley EMM (2017) Probiotics in inflammatory bowel disease. Gastroenterol Clin N Am 46:769–782Google Scholar
  2. Alard J, Peucelle V, Boutillier D, Breton J, Kuylle S, Pot B, Holowacz S, Grangette C (2018) New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches. Benef Microb 9:317–331Google Scholar
  3. Basson AR, Lam M, Cominelli F (2017) Complementary and alternative medicine strategies for therapeutic gut microbiota modulation in inflammatory bowel disease and their next-generation approaches. Gastroenterol Clin N Am 46:689–729Google Scholar
  4. Bourreille A, Cadiot G, Le Dreau G, Laharie D, Beaugerie L, Dupas JL, Marteau P, Rampal P, Moyse D, Saleh A, Le Guern ME, Galmiche JP, Group FS (2013) Saccharomyces boulardii does not prevent relapse of Crohn’s disease. Clin Gastroenterol Hepatol 11:982–987PubMedGoogle Scholar
  5. Bousvaros A, Guandalini S, Baldassano RN, Botelho C, Evans J, Ferry GD, Goldin B, Hartigan L, Kugathasan S, Levy J, Murray KF, Oliva-Hemker M, Rosh JR, Tolia V, Zholudev A, Vanderhoof JA, Hibberd PL (2005) A randomized, double-blind trial of lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis 11:833–839PubMedGoogle Scholar
  6. Chassaing B, Darfeuille-Michaud A (2011) The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140:1720–1728Google Scholar
  7. Conte MP, Schippa S, Zamboni I, Penta M, Chiarini F, Seganti L, Osborn J, Falconieri P, Borrelli O, Cucchiara S (2006) Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut 55:1760–1767PubMedPubMedCentralGoogle Scholar
  8. Derwa Y, Gracie DJ, Hamlin PJ, Ford AC (2017) Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther 46:389–400PubMedGoogle Scholar
  9. Duricova D, Burisch J, Jess T, Gower-Rousseau C, Lakatos PL, On Behalf of ECCO-EpiCom (2014) Age-related differences in presentation and course of inflammatory bowel disease: an update on the population-based literature. J Crohns Colitis 8:1351PubMedGoogle Scholar
  10. Fiorucci S, Distrutti E, Mencarelli A, Barbanti M, Palazzini E, Morelli A (2002) Inhibition of intestinal bacterial translocation with rifaximin modulates lamina propria monocytic cells reactivity and protects against inflammation in a rodent model of colitis. Digestion 66:246–256Google Scholar
  11. Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17:179–184PubMedGoogle Scholar
  12. Ganji-Arjenaki M, Rafieian-Kopaei M (2018) Probiotics are a good choice in remission of inflammatory bowel diseases: a meta analysis and systematic review. J Cell Physiol 233:2091–2103PubMedGoogle Scholar
  13. Gosiewski T, Strus M, Fyderek K, Kowalska-Duplaga K, Wedrychowicz A, Jedynak-Wasowicz U, Sladek M, Pieczarkowski S, Adamski P, Heczko PB (2012) Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 54:20–27PubMedGoogle Scholar
  14. Guslandi M, Mezzi G, Sorghi M, Testoni PA (2000) Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 45:1462–1464PubMedGoogle Scholar
  15. Henker J, Muller S, Laass MW, Schreiner A, Schulze J (2008) Probiotic Escherichia coli Nissle 1917 (EcN) for successful remission maintenance of ulcerative colitis in children and adolescents: an open-label pilot study. Z Gastroenterol 46:874–875PubMedGoogle Scholar
  16. Huynh HQ, Debruyn J, Guan L, Diaz H, Li M, Girgis S, Turner J, Fedorak R, Madsen K (2009) Probiotic preparation De Simone Formulation induces remission in children with mild to moderate acute ulcerative colitis: a pilot study. Inflamm Bowel Dis 15:760–768PubMedGoogle Scholar
  17. Jeon SR, Chai J, Kim C, Lee CH (2018) Current evidence for the management of inflammatory bowel diseases using fecal microbiota transplantation. Curr Infect Dis Rep 20:21PubMedGoogle Scholar
  18. Kellermayer R, Mir SA, Nagy-Szakal D, Cox SB, Dowd SE, Kaplan JL, Sun Y, Reddy S, Bronsky J, Winter HS (2012) Microbiota separation and C-reactive protein elevation in treatment-naive pediatric granulomatous Crohn disease. J Pediatr Gastroenterol Nutr 55:243–250PubMedGoogle Scholar
  19. Kim DH, Kim S, Lee JH, Kim JH, Che X, Ma HW, Seo DH, Kim TI, Kim WH, Kim SW, Cheon JH (2018) Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress. J Gastroenterol Hepatol. Scholar
  20. Lane ER, Lee D, Suskind DL (2017) Dietary therapies in pediatric inflammatory bowel disease: an evolving inflammatory bowel disease paradigm. Gastroenterol Clin North Am 46:731–744PubMedGoogle Scholar
  21. Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517PubMedGoogle Scholar
  22. Mack DR (2011) Probiotics in inflammatory bowel diseases and associated conditions. Nutrients 3:245–264PubMedPubMedCentralGoogle Scholar
  23. Manichanh C, Rigottier-Gois L, bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211PubMedPubMedCentralGoogle Scholar
  24. Mardini HE, Grigorian AY (2014) Probiotic mix De Simone Formulation is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis. Inflamm Bowel Dis 20:1562–1567PubMedGoogle Scholar
  25. Martinez C, Antolin M, Santos J, Torrejon A, Casellas F, Borruel N, Guarner F, Malagelada JR (2008) Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 103:643–648PubMedGoogle Scholar
  26. Mcilroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold GL (2018) Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment Pharmacol Ther 47:26–42PubMedGoogle Scholar
  27. Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A (2009) Effect of a probiotic preparation (De Simone Formulation) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol 104:437–443Google Scholar
  28. Miele E, Shamir R, Aloi M, Assa A, Braegger C, Bronsky J, De Ridder L, Escher JC, Hojsak I, Kolacek S, Koletzko S, Levine A, Lionetti P, Martinelli M, Ruemmele F, Russell RK, Boneh RS, Van Limbergen J, Veereman G, Staiano A (2018) Nutrition in pediatric inflammatory bowel disease: a position paper on behalf of the porto inflammatory bowel disease group of the European Society of pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr 66:687–708PubMedGoogle Scholar
  29. Ni J, Wu GD, Albenberg L, Tomov VT (2017) Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol 14:573–584PubMedPubMedCentralGoogle Scholar
  30. Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A (2018) Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol 11:1–10PubMedGoogle Scholar
  31. Oelschlaeger TA (2010) Mechanisms of probiotic actions – a review. Int J Med Microbiol 300:57–62PubMedGoogle Scholar
  32. Oliva S, Di Nardo G, Ferrari F, Mallardo S, Rossi P, Patrizi G, Cucchiara S, Stronati L (2012) Randomised clinical trial: the effectiveness of lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis. Aliment Pharmacol Ther 35:327–334PubMedPubMedCentralGoogle Scholar
  33. Orel R, Kamhi Trop T (2014) Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World J Gastroenterol 20:11505–11524PubMedPubMedCentralGoogle Scholar
  34. Ott SJ, Schreiber S (2006) Reduced microbial diversity in inflammatory bowel diseases. Gut 55:1207PubMedPubMedCentralGoogle Scholar
  35. Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Folsch UR, Timmis KN, Schreiber S (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53:685–693PubMedPubMedCentralGoogle Scholar
  36. Petersen AM, Mirsepasi H, Halkjaer SI, Mortensen EM, Nordgaard-Lassen I, Krogfelt KA (2014) Ciprofloxacin and probiotic Escherichia coli nissle add-on treatment in active ulcerative colitis: a double-blind randomized placebo controlled clinical trial. J Crohns Colitis 8:1498–1505PubMedGoogle Scholar
  37. Prosberg M, Bendtsen F, Vind I, Petersen AM, Gluud LL (2016) The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis. Scand J Gastroenterol 51:1407–1415PubMedGoogle Scholar
  38. Rodriguez-Nogales A, Algieri F, Garrido-Mesa J, Vezza T, Utrilla MP, Chueca N, Fernandez-Caballero JA, Garcia F, Rodriguez-Cabezas ME, Galvez J (2018) The administration of Escherichia coli nissle 1917 ameliorates development of DSS-induced colitis in mice. Front Pharmacol 9:468PubMedPubMedCentralGoogle Scholar
  39. Scaldaferri F, Gerardi V, Mangiola F, Lopetuso LR, Pizzoferrato M, Petito V, Papa A, Stojanovic J, Poscia A, Cammarota G, Gasbarrini A (2016) Role and mechanisms of action of Escherichia coli nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update. World J Gastroenterol 22:5505–5511PubMedPubMedCentralGoogle Scholar
  40. Scharl M, Rogler G (2012) Inflammatory bowel disease pathogenesis: what is new? Curr Opin Gastroenterol 28:301–309PubMedGoogle Scholar
  41. Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, Marteau P, Jian R, Dore J (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn’s disease of the colon. Gut 52:237–242PubMedPubMedCentralGoogle Scholar
  42. Singh S, Stroud AM, Holubar SD, Sandborn WJ, Pardi DS (2015) Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev:CD001176.
  43. Sivananthan K, Petersen AM (2018) Review of saccharomyces boulardii as a treatment option in IBD. Immunopharmacol Immunotoxicol:1–11. Scholar
  44. Sokol H, Seksik P, Rigottier-Gois L, Lay C, Lepage P, Podglajen I, Marteau P, Dore J (2006) Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis 12:106–111PubMedGoogle Scholar
  45. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M, Lochs H (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122:44–54Google Scholar
  46. Zuo T, Ng SC (2018) The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Front Microbiol 9:2247PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Section of Gastroenterology, Hepatology and Nutrition Department of PediatricsUniversity of ChicagoChicagoUSA

Personalised recommendations