Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome

Alimentary Pharmacology and Therapeutics

Volumn 48, Issue 10, 2018, Pages 1044-1060

  Ford, Alexander C ^a,b   Harris, Lucinda A ^c   Lacy, Brian E ^d   Quigley, Eamonn M  M ^e   Moayyedi, Paul ^f  

^a ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

^b UNIVERSITY OF LEEDS   (United Kingdom)

^c MAYO CLINIC COLLEGE OF MEDICINE   (United States)

^d MAYO CLINIC   (United States)

^e WEILL CORNELL MEDICAL COLLEGE   (United States)

^f MCMASTER UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; GASTROINTESTINAL AGENT; PREBIOTIC AGENT; PROBIOTIC AGENT; RIFAXIMIN; SYNBIOTIC AGENT;

ABDOMINAL PAIN; ADULT; DRUG EFFECT; HUMAN; INTESTINE FLORA; IRRITABLE COLON; META ANALYSIS; PHYSIOLOGY; PROCEDURES; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT OUTCOME;

ABDOMINAL PAIN; ADULT; ANTI-BACTERIAL AGENTS; GASTROINTESTINAL AGENTS; GASTROINTESTINAL MICROBIOME; HUMANS; IRRITABLE BOWEL SYNDROME; PREBIOTICS; PROBIOTICS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RIFAXIMIN; SYNBIOTICS; TREATMENT OUTCOME;

EID: 85054477412     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/apt.15001     Document Type: Review

References (104)

1. Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med. 2017;376:2566-2578.
2. Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150:1393-1407.
3. Ford AC, Forman D, Bailey AG, Axon ATR, Moayyedi P. Irritable bowel syndrome: a 10-year natural history of symptoms, and factors that influence consultation behavior. Am J Gastroenterol. 2008;103:1229-1239.
4. Lovell RM, Ford AC. Global prevalence of, and risk factors for, irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:712-721.
5. Palsson OS, Whitehead WE, van Tilburg MA, et al. Rome IV diagnostic questionnaires and tables for investigators and clinicians. Gastroenterology. 2016;150:1481-1491.
6. Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol. 2016;1:133-146.
7. Marshall JK, Thabane M, Borgaonkar MR, James C. Postinfectious irritable bowel syndrome after a food-borne outbreak of gastroenteritis attributed to a viral pathogen. Clin Gastroenterol Hepatol. 2007;5:457-460.
8. Marshall JK, Thabane M, Garg AX, et al. Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology. 2006;131:445-450.
9. Lin HC. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004;292:852-858.
10. Durban A, Abellan JJ, Jimenez-Hernandez N, et al. Instability of the faecal microbiota in diarrhoea-predominant irritable bowel syndrome. FEMS Microbiol Ecol. 2013;86:581-589.
11. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhoea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24:521-530; e248.
12. Jalanka-Tuovinen J, Salojarvi J, Salonen A, et al. Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut. 2014;63:1737-1745.
13. Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133:24-33.
14. Jeffery IB, O'Toole PW, Ohman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61:997-1006.
15. Tap J, Derrien M, Tornblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152:111-123; e8.
16. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491-502.
17. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506-514.
18. Yu D, Cheeseman F, Vanner S. Combined oro-caecal scintography and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut. 2011;60:334-340.
19. Posserud I, Stotzer PO, Bjornsson ES, Abrahamsson H, Simren M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56:802-808.
20. Ford AC, Spiegel BMR, Talley NJ, Moayyedi P. Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2009;7:1279-1286.
21. Williams MD, Ha CY, Ciorba MA. Probiotics as therapy in gastroenterology: a study of physician opinions and recommendations. J Clin Gastroenterol. 2010;44:631-636.
22. Moayyedi P, Ford AC, Brandt LJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010;59:325-332.
23. Ford AC, Quigley EM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1547-1561.
24. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2-S26.
25. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based systematic review on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(suppl I):S8-S35.
26. Ford AC, Moayyedi P, Chey WD, et al. American College of Gastroenterology monograph on management of irritable bowel syndrome. Am J Gastroenterol. 2018;113(Suppl 2):1-18.
27. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions: Version 5.1.0. www.cochrane-handbook.org 2009. Accessed April 6, 2018.
28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188.
29. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-1558.
30. Egger M, Davey-Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629-634.
31. Sterne JA, Sutton AJ, Ioannidis JP, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.
32. Kabir MA, Ishaque SM, Ali MS, Mahmuduzzaman M, Hasan M. Role of Saccharomyces boulardii in diarrhoea predominant irritable bowel syndrome. Mymensingh Med J. 2011;20:397-401.
33. Ko SJ, Han G, Kim SK, et al. Effect of Korean herbal medicine combined with a probiotic mixture on diarrhoea-dominant irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Evid Based Complement Alternat Med. 2013;2013:824605.
34. Stevenson C, Blaauw R, Fredericks E, Visser J, Roux S. Randomized clinical trial: effect of Lactobacillus plantarum 299 v on symptoms of irritable bowel syndrome. Nutrition (Burbank, Los Angeles County, Calif.) 2014;30:1151-1157.
35. Sisson G, Ayis S, Sherwood RA, Bjarnason I. Randomised clinical trial: a liquid multi-strain probiotic vs. placebo in the irritable bowel syndrome–a 12 week double-blind study. Aliment Pharmacol Ther. 2014;40:51-62.
36. Jafari E, Vahedi H, Merat S, Momtahen S, Riahi A. Therapeutic effects, tolerability and safety of a multi-strain probiotic in Iranian adults with irritable bowel syndrome and bloating. Arch Iran Med. 2014;17:466-470.
37. Ludidi S, Jonkers DM, Koning CJ, et al. Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients. Neurogastroenterol Motil. 2014;26:705-714.
38. Yoon JS, Sohn W, Lee OY, et al. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014;29:52-59.
39. Abbas Z, Yakoob J, Jafri W, et al. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial. Eur J Gastroenterol Hepatol. 2014;26:630-639.
40. Lorenzo-Zuniga V, Llop E, Suarez C, et al. I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life. World J Gastroenterol. 2014;20:8709-8716.
41. Pineton de Chambrun G, Neut C, Chau A, et al. A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome. Dig Liver Dis. 2015;47:119-124.
42. Wong RK, Yang C, Song GH, Wong J, Ho KY. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Dig Dis Sci. 2015;60:186-194.
43. Yoon H, Park YS, Lee DH, Seo JG, Shin CM, Kim N. Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Biochem Nutr. 2015;57:129-134.
44. Thijssen AY, Clemens CH, Vankerckhoven V, Goossens H, Jonkers DM, Masclee AA. Efficacy of Lactobacillus casei Shirota for patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2016;28:8-14.
45. Spiller R, Pelerin F, Cayzeele Decherf A, et al. Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation. United European Gastroenterol J. 2016;4:353-362.
46. Hod K, Sperber AD, Ron Y, et al. A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS. Neurogastroenterol Motil. 2017;29. https://doi.org/10.1111/nmo.13037
47. Pinto-Sanchez MI, Hall GB, Ghajar K, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153:448-459.
48. Lyra A, Hillila M, Huttunen T, et al. Irritable bowel syndrome symptom severity improves equally with probiotic and placebo. World J Gastroenterol. 2016;22:10631-10642.
49. Staudacher HM, Lomer MCE, Farquharson FM, et al. Diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and probiotic restores Bifidobacterium species: a randomized controlled trial. Gastroenterology. 2017;153:936-947.
50. Olesen M, Gudmand-Hoyer E. Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome. Am J Clin Nutr. 2000;72:1570-1575.
51. Azpiroz F, Dubray C, Bernalier-Donadille A, et al. Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study. Neurogastroenterol Motil 2017;29. https://doi.org/10.1111//nmo.12911
52. Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:508-518.
53. Gade J, Thorn P. Paraghurt for patients with irritable bowel syndrome. Scand J Prim Health Care. 1989;7:23-26.
54. Nobaek S, Johansson ML, Molin G, Ahrne S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231-1238.
55. Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2001;13:1143.
56. Kim HJ, Camilleri M, McKinzie S, et al. A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2003;17:895-904.
57. Kajander K, Hatakka K, Poussa T, Farkkila M, Korpela R. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther. 2005;22:387-394.
58. Kim HJ, Vazquez Roque MI, 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.
59. Niv E, Naftali T, Hallak R, Vaisman N. The efficacy of Lactobacillus reuteri ATCC 55730 in the treatment of patients with irritable bowel syndrome—a double blind, placebo-controlled, randomized study. Clin Nutr. 2005;24:925-931.
60. O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541-551.
61. Kim YG, Moon JT, Lee KM, Chon NR, Park H. The effects of probiotics on symptoms of irritable bowel syndrome. Korean J Gastroenterol. 2006;47:413-419.
62. Simren M, Syrous A, Lindh A, Abrahamsson H. Effects of Lactobacillus plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowel syndrome (IBS)—a randomized double blind controlled trial. Gastroenterology. 2006;130(suppl 1):A600.
63. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:1581-1590.
64. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double blind, controlled trial. Aliment Pharmacol Ther. 2007;26:475-486.
65. Drouault-Holowacz S, Bieuvelet S, Burckel A, Cazaubiel M, Dray X, Marteau P. A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol. 2008;32:147-152.
66. Enck P, Zimmerman K, Menke G, Muller-Lissner S, Martens U, Klosterhalfen S. A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome—a randomized controlled trial with primary care physicians. Neurogastroenterol Motil. 2008;20:1103-1109.
67. Kajander K, Myllyluoma E, Rajilic-Stojanovic M, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther. 2008;27:48-57.
68. Sinn DH, Song JH, Kim HJ, et al. Therapeutic effect of Lactobacillus acidophilus -SDC 2012, 2013 in patients with irritable bowel syndrome. Dig Dis Sci. 2008;53:2714-2718.
69. Zeng J, Li YQ, Zuo XL, Zhen YB, Yang J, Liu CH. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28:994-1002.
70. Agrawal A, Houghton LA, Morris J, et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2009;29:104-114.
71. Enck P, Zimmerman K, Menke G, Klosterhalfen S. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009;47:209-214.
72. Hong KS, Kang HW, Im JP, et al. Effect of probiotics on symptoms in Korean adults with irritable bowel syndrome. Gut Liv. 2009;3:101-107.
73. Williams EA, Stimpson J, Wang D, et al. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2009;29:97-103.
74. Simren M, Ohman L, Olsson J, et al. Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome—a randomized, double-blind, controlled study. Aliment Pharmacol Ther. 2010;31:218-227.
75. Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ. A randomized, double-blind, placebo-controlled multicenter trial of Saccharomyces boulardii in irritable bowel syndrome: effect on quality of life. J Clin Gastroenterol. 2011;45:679-683.
76. Guglielmetti S, Mora D, Gschwender M, Popp K. Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:1123-1132.
77. Michail S, Kenche H. Gut microbiota is not modified by randomized, double-blind, placebo-controlled trial of VSL#3 in diarrhea-predominant irritable bowel syndrome. Probiotics Antimicrob Proteins. 2011;3:1-7.
78. Ringel-Kulka T, Palsson OS, Maier D, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011;45:518-525.
79. Sondergaard B, Olsson J, Ohlson K, Svensson U, Bytzer P, Ekesbo R. Effects of probiotic fermented milk on symptoms and intestinal flora in patients with irritable bowel syndrome: a randomized, placebo-controlled trial. Scand J Gastroenterol. 2011;46:663-672.
80. Cha BK, Jung SM, Choi CH, et al. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2012;46:220-227.
81. Cui S, Hu Y. Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Int J Clin Exp Med. 2012;5:238-244.
82. Dapoigny M, Piche T, Ducrotte P, Lunaud B, Cardot JM, Bernalier-Donadille A. Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study. World J Gastroenterol. 2012;18:2067-2075.
83. Ducrotte P, Sawant P, Jayanthi V. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012;18:4012-4018.
84. Farup PG, Jacobsen M, Ligaarden SC, Rudi K. Probiotics, symptoms, and gut microbiota: what are the relations? A randomized controlled trial in subjects with irritable bowel syndrome. Gastroenterol Res Pract. 2012;2012:214102.
85. Kruis W, Chrubasik S, Boehm S, Stange S, Schulze J. A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel syndrome. Int J Colorectal Dis. 2012;27:467-474.
86. Begtrup LM, de Muckadell OB, Kjeldsen J, Christensen RD, Jarbol DE. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome—a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol. 2013;48:1127-1135.
87. Roberts LM, McCahon D, Holder R, Wilson S, Hobbs FD. A randomised controlled trial of a probiotic ‘functional food’ in the management of irritable bowel syndrome. BMC Gastroenterol. 2013;13:45.
88. Tsuchiya J, Barreto R, Okura R, Kawakita S, Fesce E, Marotta F. Single-blind follow up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome. Chin J Dig Dis. 2004;5:169-174.
89. Min YW, Park SU, Jang YS, et al. Effect of composite yogurt enriched with acacia fiber and Bifidobacterium lactis. World J Gastroenterol. 2012;18:4563-4569.
90. Ghoshal UC, Srivastava D, Misra A, Ghoshal U. A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial. Eur J Gastroenterol Hepatol. 2016;28:281-289.
91. Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151:1113-1121.
92. Lombardo L, Schembri M. A reason why lactose-free diet can be clinically ineffective in lactose intolerance patients. United European Gastroenterol J 2015;3(Suppl 1):A54.
93. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412-419.
94. Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhaji I. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006;101:326-333.
95. Pimentel M, Park S, Mirocha J, Kane SV, Kong Y. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006;145:557-563.
96. Lembo A, Zakko SF, Ferreira NL, et al. Rifaximin for the treatment of diarrhea-associated irritable bowel syndrome: short term treatment leading to long term sustained response. Gastroenterology. 2008;134(suppl 1):A545.
97. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22-32.
98. Schoenfeld P, Pimentel M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials. Aliment Pharmacol Ther. 2014;39:1161-1168.
99. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000;95:3503-3506.
100. Acosta A, Camilleri M, Shin A, et al. Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome. Clin Transl Gastroenterol. 2016;7:e173.
101. Zeber-Lubecka N, Kulecka M, Ambrozkiewicz F, et al. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome. Gut Microbes. 2016;7:397-413.
102. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309-325.
103. Ringel-Kulka T, Goldsmith JR, Carroll IM, et al. Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain—a randomised clinical study. Aliment Pharmacol Ther. 2014;40:200-207.
104. Rousseaux C, Thuru X, Gelot A, et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med. 2007;13:35-37.