Modification of the Gut Microbiome to Maintain Health or Treat Disease| Volume 146, ISSUE 6, P1554-1563, May 01, 2014

Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

  • Fergus Shanahan
    Reprint requests Address requests for reprints to: Fergus Shanahan, MD, DSc, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. fax: (353) 21-4345300.
    Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland

    Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland
    Search for articles by this author
  • Eamonn M.M. Quigley
    Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland

    Division of Gastroenterology and Hepatology, Houston Methodist, Houston, Texas
    Search for articles by this author
Published:January 30, 2014DOI:
      There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms. We assess the rationale for modulating the microbiota for treatment of IBD and IBS, and discuss whether current concepts are simplistic and overstated or simply under-researched. Are claims exaggerated and expectations unrealistic? Difficulties with microbiota terminology and technologies, as well as differences among patients and the heterogeneity of these diseases, pose additional challenges in developing microbiota-based therapies for IBD and IBS.


      Abbreviations used in this paper:

      IBD (inflammatory bowel disease), IBS (irritable bowel syndrome)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Shanahan F.
        The gut microbiota–a clinical perspective on lessons learned.
        Nat Rev Gastroenterol Hepatol. 2012; 9: 609-614
        • Wallace B.D.
        • Wang H.
        • Lane K.T.
        • et al.
        Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.
        Science. 2010; 330: 831-835
        • Shanahan F.
        Probiotics in perspective.
        Gastroenterology. 2010; 139: 1808-1812
        • Shanahan F.
        • Dinan T.G.
        • Ross P.
        • et al.
        Probiotics in transition.
        Clin Gastroenterol Hepatol. 2012; 10: 1220-1224
        • Shanahan F.
        The microbiota in inflammatory bowel disease: friend, bystander, and sometime-villain.
        Nutr Rev. 2012; 70: S31-S37
        • Preidis G.A.
        • Versalovic J.
        Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era.
        Gastroenterology. 2009; 136: 2015-2031
        • Moayyedi P.
        • Ford A.C.
        • Talley N.J.
        • et al.
        The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.
        Gut. 2010; 59: 325-332
        • Nikfar S.
        • Rahimi R.
        • Rahimi F.
        • et al.
        Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials.
        Dis Colon Rectum. 2008; 51: 1775-1780
        • McFarland L.V.
        • Dublin S.
        Meta-analysis of probiotics for the treatment of irritable bowel syndrome.
        World J Gastroenterol. 2008; 14: 2650-2661
        • Brenner D.M.
        • Moeller M.J.
        • Chey W.D.
        • et al.
        The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review.
        Am J Gastroenterol. 2009; 104: 1033-1049
        • Rolfe V.E.
        • Fortun P.J.
        • Hawkey C.J.
        • et al.
        Probiotics for maintenance of remission in Crohn's disease.
        Cochrane Database Syst Rev. 2006; 4: CD004826
        • Rahimi R.
        • Nikfar S.
        • Rahimi F.
        • et al.
        A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease.
        Dig Dis Sci. 2008; 53: 2524-2531
        • Shen J.
        • Ran H.Z.
        • Yin M.H.
        • et al.
        Meta-analysis: the effect and adverse events of Lactobacilli versus placebo in maintenance therapy for Crohn disease.
        Intern Med J. 2009; 39: 103-109
        • Doherty G.
        • Bennett G.
        • Patil S.
        • et al.
        Interventions for prevention of post-operative recurrence of Crohn's disease.
        Cochrane Database Syst Rev. 2009; 4: CD006873
        • Doherty G.A.
        • Bennett G.C.
        • Cheifetz A.S.
        • et al.
        Meta-analysis: targeting the intestinal microbiota in prophylaxis for post-operative Crohn's disease.
        Aliment Pharmacol Ther. 2010; 31: 802-809
        • Sang L.X.
        • Chang B.
        • Zhang W.L.
        • et al.
        Remission induction and maintenance effect of probiotics on ulcerative colitis: a meta-analysis.
        World J Gastroenterol. 2010; 16: 1908-1915
        • Naidoo K.
        • Gordon M.
        • Fagbemi A.O.
        • et al.
        Probiotics for maintenance of remission in ulcerative colitis.
        Cochrane Database Syst Rev. 2011; 12: CD007443
      1. Orwell G. Politics of the English language. 1946. Available at: Accessed Dec 17, 2013.

        • FAO/WHO
        Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Report of a joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria.
        World Health Organization, Basel, Switzerland2001
        • Cadwell K.
        • Patel K.K.
        • Maloney N.S.
        • et al.
        Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine.
        Cell. 2010; 141: 1135-1145
        • Hand T.H.
        • Dos Santos L.M.
        • Bouladoux N.
        • et al.
        Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.
        Science. 2012; 337: 1553-1556
        • Bothin C.
        • Midtvedt T.
        The role of gastrointestinal microflora in postsurgical adhesion formation–a study in germfree rats.
        Eur Surg Res. 1992; 24: 309-312
        • Mourelle M.
        • Salas A.
        • Guarner F.
        • et al.
        Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis.
        Gastroenterology. 1998; 114: 519-526
        • Van Tol E.A.F.
        • Holt L.
        • Ling Li F.
        • et al.
        Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts.
        Am J Physiol. 1999; 277: G245-G255
        • Rigby R.J.
        • Hunt M.R.
        • Scull B.P.
        • et al.
        A new animal model of postsurgical bowel inflammation and fibrosis: the effect of commensal microflora.
        Gut. 2009; 58: 1104-1112
        • Shanahan F.
        The colonic microbiota in health and disease.
        Curr Opin Gastroenterol. 2013; 29: 49-54
        • Whitehead W.E.
        • Engel B.T.
        • Schuster M.M.
        Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients.
        Dig Dis Sci. 1980; 25: 404-413
        • Longstreth G.F.
        • Thompson W.G.
        • Chey W.D.
        • et al.
        Functional bowel disorders.
        Gastroenterology. 2006; 130: 1480-1491
        • Quigley E.M.
        Bugs on the brain; brain in the gut-seeking explanations for common gastrointestinal symptoms.
        Ir J Med Sci. 2012; 182: 1-6
        • Quigley E.M.
        Bacterial flora in irritable bowel syndrome: role in pathophysiology, implications for management.
        J Dig Dis. 2007; 8: 2-7
        • Suzuki H.
        • Moayyedi P.
        Helicobacter pylori infection in functional dyspepsia.
        Nat Rev Gastroenterol Hepatol. 2013; 10: 168-174
        • Villarreal A.A.
        • Aberger F.J.
        • Benrud R.
        • et al.
        Use of broad-spectrum antibiotics and the development of irritable bowel syndrome.
        WMJ. 2012; 111: 17-20
        • Pimentel M.
        • Chow E.J.
        • Lin H.C.
        Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.
        Am J Gastroenterol. 2000; 95: 3503-3506
        • Jeffery I.B.
        • Quigley E.M.
        • Ohman L.
        • et al.
        The microbiota link to irritable bowel syndrome: an emerging story.
        Gut Microbes. 2012; 3: 572-576
        • Carroll I.M.
        • Ringel-Kulka T.
        • Keku T.O.
        • et al.
        Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome.
        Am J Physiol Gastrointest Liver Physiol. 2011; 301: G799-G807
        • Jeffery I.B.
        • O'Toole P.W.
        • Öhman L.
        • et al.
        An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.
        Gut. 2012; 61: 997-1006
        • Duboc H.
        • Rainteau D.
        • Rajca S.
        • et al.
        Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome.
        Neurogastroenterol Motil. 2012; 24 (e246–e247): 513-520
        • Manichanh C.
        • Eck A.
        • Varela E.
        • et al.
        Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet.
        Gut. 2014; 63: 401-408
        • Macfarlane G.T.
        • Macfarlane S.
        Bacteria, colonic fermentation, and gastrointestinal health.
        J AOAC Int. 2012; 95: 50-60
        • Quigley E.M.M.
        Therapies aimed at the gut microbiota and inflammation. Antibiotics, probiotics/prebiotics/synbiotics, anti-inflammatory therapies.
        Gastroenterol Clin North Am. 2011; 40: 207-222
        • Pimentel M.
        • Lembo A.
        • Chey W.D.
        • et al.
        Rifaximin therapy for patients with irritable bowel syndrome without constipation.
        N Engl J Med. 2011; 364: 22-32
        • Cryan J.F.
        • O'Mahony S.M.
        The microbiome-gut-brain axis: from bowel to behavior.
        Neurogastroenterol Motil. 2011; 23: 187-192
        • Hviid A.
        • Svanström H.
        • Frisch M.
        Antibiotic use in inflammatory bowel diseases in childhood.
        Gut. 2011; 60: 49-54
        • Shaw S.Y.
        • Blanchard J.F.
        • Bernstein C.N.
        Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease.
        Am J Gastroenterol. 2010; 105: 2687-2692
        • Collins S.M.
        The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders.
        Gastroenterology. 1996; 111: 1683-1699
        • Barbara G.
        • Stanghellini V.
        • Brandi G.
        • et al.
        Interactions between commensal gut flora and gut sensorimotor function in health and disease.
        Am J Gastroenterol. 2005; 100: 2560-2568
        • Agrawal A.
        • Houghton L.A.
        • Morris J.
        • et al.
        Clinical trial: the effects of a fermented milk product containing bifidobacteriumlactis DN-173-010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation.
        Aliment Pharmacol Ther. 2009; 29: 104-114
        • Kim H.J.
        • Camilleri M.
        • McKinzie S.
        • et al.
        A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.
        Aliment Pharmacol Ther. 2003; 17: 895-904
        • Kim H.J.
        • Vazquez Roque M.I.
        • Camilleri M.
        • et al.
        A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.
        Neurogastroenterol Motil. 2005; 17: 687-696
        • Tillisch K.
        • Labus J.
        • Kilpatrick L.
        • et al.
        Consumption of fermented milk product with probiotic modulates brain activity.
        Gastroenterology. 2013; 144: 1394-1401
        • Groeger D.
        • O'Mahoney L.
        • Murphy E.F.
        • et al.
        Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut.
        Gut Microbes. 2013; 4: 325-339
        • Khan W.I.
        • Collins S.M.
        Gut motor inflammation: immunological control in enteric infection and inflammation.
        Clin Exp Immunol. 2005; 143: 389-397
        • Thomas C.M.
        • Versalovic J.
        Probiotics-host communication: modulation of signaling pathways in the intestine.
        Gut Microbes. 2010; 1: 148-163
        • O'Mahony S.M.
        • Marchesi J.R.
        • Scully P.
        • et al.
        Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses.
        Biol Psychiatry. 2009; 65: 263-267
        • O'Mahony S.M.
        • Savignac H.M.
        • O'Brien T.
        • et al.
        Early-life dysbiosis-induced visceral hypersensitivity in adulthood.
        Gastroenterology. 2010; 138: S4-S5
        • Spiller R.
        • Lam C.
        An update on post-infectious irritable bowel syndrome: role of genetics, immune activation, serotonin and altered microbiome.
        J Neurogastroenterol Motil. 2012; 18: 258-268
        • Quigley E.M.
        • Flourie B.
        Probiotics and irritable bowel syndrome: a rationale for their use and an assessment of the evidence to date.
        Neurogastroenterol Motil. 2007; 19: 166-172
        • Quigley E.M.M.
        Probiotics in gastrointestinal disorders.
        Hosp Pract. 2010; 38: 122-129
        • Andriulli A.
        • Neri M.
        • Loguercio C.
        • et al.
        Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in patients with irritable bowel syndrome: a multicenter, randomized study.
        J Clin Gastroenterol. 2008; 42: S218-S223
        • Shanahan F.
        A commentary on the safety of probiotics.
        Gastroenterol Clin North Am. 2012; 41: 869-876
        • Anderson J.L.
        • Edney R.J.
        • Whelan K.
        Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease.
        Aliment Pharmacol Ther. 2012; 36: 503-516
        • Damman C.J.
        • Miller S.I.
        • Surawicz C.M.
        • et al.
        The microbiome and inflammatory bowel disease: is there a role for fecal microbiota transplantation?.
        Am J Gastroenterol. 2012; 107: 1452-1459
        • Brandt L.J.
        • Aroniadis O.C.
        An overview of fecal microbiota transplantation: techniques, indications, and outcomes.
        Gastrointest Endosc. 2013; 78: 240-249
        • Shanahan F.
        Gut microbes: from bugs to drugs.
        Am J Gastroenterol. 2012; 105: 275-279
        • Kuss S.K.
        • Best G.T.
        • Etheredge C.A.
        • et al.
        Intestinal microbiota promote enteric virus replication and systemic pathogenesis.
        Science. 2011; 334: 249-252
        • Virgin H.V.
        • Todd J.A.
        Metagenomics and personalized medicine.
        Cell. 2011; 147: 44-56