Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper. 1. Introduction Functional bowel disorders, including irritable bowel syndrome (IBS), are common gastrointestinal disorders all over the world. Previously, IBS was thought to be a psychosomatic disorder. However, in the last few decades, advances in our understanding of the pathophysiology of IBS have revealed several factors, including alterations in the microbiota, as potentially relevant to the cause of this syndrome and the precipitation of its symptoms. Indeed, alterations in the gut microbiota are being increasingly implicated in the pathogenesis of several gastrointestinal and systemic diseases. We wish, therefore, to review the gut microbiota and its alterations in, and relationships to, IBS. 2. Gut Microbiota in Health The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as the digestion of food, metabolism of the drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall and maintenance of homeostasis in the gastrointestinal tract (GIT) [1–3]. The human gut is first colonized at birth; this microbiota gradually increases in size and diversity up to the end of the first year of life; by that time, the gut microbiota has come to resemble that of the adult and remains relatively stable thereafter [4]. The composition of the gut microbiota varies
References
[1]
K. Ponnusamy, J. N. Choi, J. Kim, S.-Y. Lee, and C. H. Lee, “Microbial community and metabolomic comparison of irritable bowel syndrome faeces,” Journal of Medical Microbiology, vol. 60, no. 6, pp. 817–827, 2011.
[2]
E. M. M. Quigley and R. Quera, “Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics,” Gastroenterology, vol. 130, no. 2, supplement 1, pp. S78–S90, 2006.
[3]
S. Prakash, L. Rodes, M. Coussa-Charley, et al., “Gut microbiota: next frontier in understanding human health and development of biotherapeutics,” Biologics, vol. 5, pp. 71–86, 2011.
[4]
I. Sekirov, S. L. Russell, L. Caetano M Antunes, and B. B. Finlay, “Gut microbiota in health and disease,” Physiological Reviews, vol. 90, no. 3, pp. 859–904, 2010.
[5]
M. Carrara, S. Desideri, M. Azzurro et al., “Small intestine bacterial overgrowth in patients with irritable bowel syndrome,” European Review for Medical and Pharmacological Sciences, vol. 12, no. 3, pp. 197–202, 2008.
[6]
E. Malinen, T. Rinttil？, K. Kajander et al., “Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR,” American Journal of Gastroenterology, vol. 100, no. 2, pp. 373–382, 2005.
[7]
A. S. Neish, “Microbes in gastrointestinal health and disease,” Gastroenterology, vol. 136, no. 1, pp. 65–80, 2009.
[8]
E. M. Quigley, “Do patients with functional gastrointestinal disorders have an altered gut flora?” Therapeutic Advances in Gastroenterology, vol. 2, no. 4, pp. 23–30, 2009.
[9]
J. M. Park, M. G. Choi, Y. K. Cho et al., “Functional gastrointestinal disorders diagnosed by Rome III questionnaire in Korea,” Journal of Neurogastroenterology and Motility, vol. 17, no. 3, pp. 279–286, 2011.
[10]
M. Teo, S. Chung, L. Chitti et al., “Small bowel bacterial overgrowth is a common cause of chronic diarrhea,” Journal of Gastroenterology and Hepatology, vol. 19, no. 8, pp. 904–909, 2004.
[11]
I. Posserud, A. Ersryd, and M. Simrén, “Functional findings in irritable bowel syndrome,” World Journal of Gastroenterology, vol. 12, no. 19, pp. 2830–2838, 2006.
[12]
H. Park, “The role of small intestinal bacterial overgrowth in the pathophysiology of irritable bowel syndrome,” Journal of Neurogastroenterology and Motility, vol. 16, no. 1, pp. 3–4, 2010.
[13]
J. Bures, J. Cyrany, D. Kohoutova et al., “Small intestinal bacterial overgrowth syndrome,” World Journal of Gastroenterology, vol. 16, no. 24, pp. 2978–2990, 2010.
[14]
U. C. Ghoshal, H. Park, and K. A. Gwee, “Bugs and irritable bowel syndrome: the good, the bad and the ugly,” Journal of Gastroenterology and Hepatology, vol. 25, no. 2, pp. 244–251, 2010.
[15]
M. Simrén and P. O. Stotzer, “Use and abuse of hydrogen breath tests,” Gut, vol. 55, no. 3, pp. 297–303, 2006.
[16]
A. M. Scanu, T. J. Bull, S. Cannas et al., “Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease: common neural and immune pathogenicities,” Journal of Clinical Microbiology, vol. 45, no. 12, pp. 3883–3890, 2007.
[17]
E. Malinen, L. Krogius-Kurikka, A. Lyra et al., “Association of symptoms with gastrointestinal microbiota in irritable bowel syndrome,” World Journal of Gastroenterology, vol. 16, no. 36, pp. 4532–4540, 2010.
[18]
A. Kassinen, L. Krogius-Kurikka, H. M？kivuokko et al., “The fecal microbiota of irritable Bowel syndrome patients differs significantly from that of healthy subjects,” Gastroenterology, vol. 133, no. 1, pp. 24–33, 2007.
[19]
I. M. Carroll, Y. H. Chang, J. Park, R. B. Sartor, and Y. Ringel, “Luminal and mucosal-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome,” Gut Pathogens, vol. 2, no. 1, 2010.
[20]
A. Lyra, L. Krogius-Kurikka, J. Nikkil？ et al., “Effect of a multispecies probiotic supplement on quantity of irritable bowel syndrome-related intestinal microbial phylotypes,” BMC Gastroenterology, vol. 10, p. 110, 2010.
[21]
W. G. Thompson, “The road to Rome,” Gastroenterology, vol. 130, no. 5, pp. 1552–1556, 2006.
[22]
G. C. Parkes, J. Brostoff, K. Whelan, and J. D. Sanderson, “Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment,” American Journal of Gastroenterology, vol. 103, no. 6, pp. 1557–1567, 2008.
[23]
G. K. Makharia, A. K. Verma, R. Amarchand et al., “Prevalence of irritable bowel syndrome: a community based study from northern India,” Journal of Neurogastroenterology and Motility, vol. 17, no. 1, pp. 82–87, 2011.
[24]
U. C. Ghoshal, P. Abraham, C. Bhatt et al., “Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force,” Indian Journal of Gastroenterology, vol. 27, no. 1, pp. 22–28, 2008.
[25]
K. A. Gwee, C. L. Lu, and U. C. Ghoshal, “Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed,” Journal of Gastroenterology and Hepatology, vol. 24, no. 10, pp. 1601–1607, 2009.
[26]
L. ？hman and M. Simrén, “New insights into the pathogenesis and pathophysiology of irritable bowel syndrome,” Digestive and Liver Disease, vol. 39, no. 3, pp. 201–215, 2007.
[27]
T. Karantanos, T. Markoutsaki, M. Gazouli, et al., “Current insights in to the pathophysiology of irritable Bowel syndrome,” Gut Pathogens, vol. 2, no. 1, p. 3, 2010.
[28]
E. K. Brint, J. MacSharry, A. Fanning, F. Shanahan, and E. M.M. Quigley, “Differential expression of toll-like receptors in patients with irritable bowel syndrome,” American Journal of Gastroenterology, vol. 106, no. 2, pp. 329–336, 2011.
[29]
D. A. Drossman, “The functional gastrointestinal disorders and the Rome III process,” Gastroenterology, vol. 130, no. 5, pp. 1377–1390, 2006.
[30]
B. J. Lee and Y. T. Bak, “Irritable bowel syndrome, gut microbiota and probiotics,” Journal of Neurogastroenterology and Motility, vol. 17, no. 3, pp. 252–266, 2011.
[31]
J. E. Kellow, F. Azpiroz, M. Delvaux et al., “Applied principles of neurogastroenterology: physiology/motility sensation,” Gastroenterology, vol. 130, no. 5, pp. 1412–1420, 2006.
[32]
T. Rinttil？, A. Lyra, L. Krogius-Kurikka, and A. Palva, “Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjects,” Gut Pathogens, vol. 3, no. 1, 2011.
[33]
A. P.M. Kerckhoffs, K. Ben-Amor, M. Samsom et al., “Molecular analysis of faecal and duodenal samples reveals significantly higher prevalence and numbers of Pseudomonas aeruginosa in irritable bowel syndrome,” Journal of Medical Microbiology, vol. 60, no. 2, pp. 236–245, 2011.
[34]
M. Rajili？-Stojanovi？, E. Biagi, H. G.H.J. Heilig et al., “Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome,” Gastroenterology, vol. 141, no. 5, pp. 1792–1801, 2011.
[35]
D. M. Saulnier, K. Riehle, T. -A. Mistretta et al., “Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome,” Gastroenterology, vol. 141, no. 5, pp. 1782–1791, 2011.
[36]
A. Salonen, W. M. De Vos, and A. Palva, “Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives,” Microbiology, vol. 156, no. 11, pp. 3205–3215, 2010.
[37]
G. Le Gall, S. O. Noor, K. Ridgway et al., “Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome,” Journal of Proteome Research, vol. 10, no. 9, pp. 4208–4218, 2011.
[38]
S. Vanner, “The small intestinal bacterial overgrowth. Irritable bowel syndrome hypothesis: implications for treatment,” Gut, vol. 57, no. 9, pp. 1315–1321, 2008.
[39]
A. W. DuPont, “Postinfectious irritable bowel syndrome,” Clinical Infectious Diseases, vol. 46, no. 4, pp. 594–599, 2008.
[40]
S. R. Jee, W. Morales, K. Low et al., “ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS,” World Journal of Gastroenterology, vol. 16, no. 29, pp. 3680–3686, 2010.
[41]
J. K. Marshall, M. Thabane, A. X. Garg, W. F. Clark, M. Salvadori, and S. M. Collins, “Incidence and epidemiology of irritable Bowel syndrome after a large waterborne outbreak of bacterial dysentery,” Gastroenterology, vol. 131, no. 2, pp. 445–450, 2006.
[42]
S. D. Parry, R. Stansfield, D. Jelley et al., “Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study,” American Journal of Gastroenterology, vol. 98, no. 9, pp. 1970–1975, 2003.
[43]
K. A. Gwee, J. C. Graham, M. W. McKendrick et al., “Psychometric scores and persistence of irritable bowel after infectious diarrhoea,” Lancet, vol. 347, no. 8995, pp. 150–153, 1996.
[44]
M. Thabane, D. T. Kottachchi, and J. K. Marshall, “Systematic review and meta-analysis: the incidence and prognosis of post-infectious irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 26, no. 4, pp. 535–544, 2007.
[45]
H. A. Halvorson, C. D. Schlett, M. S. Riddle, and M. Al-Haddad, “Postinfectious irritable bowel syndrome—a meta-analysis,” American Journal of Gastroenterology, vol. 101, no. 8, pp. 1894–1942, 2006.
[46]
H. L. DuPont, G. Galler, F. Garcia-Torres, A. W. DuPont, A. Greisinger, and Z. D. Jiang, “Travel and travelers' diarrhea in patients with irritable bowel syndrome,” American Journal of Tropical Medicine and Hygiene, vol. 82, no. 2, pp. 301–305, 2010.
[47]
M. Thabane and J. K. Marshall, “Post-infectious irritable bowel syndrome,” World Journal of Gastroenterology, vol. 15, no. 29, pp. 3591–3596, 2009.
[48]
S. K. Sarna, “Lessons learnt from post-infectious IBS,” Frontiers in Physiology, vol. 2, p. 49, 2011.
[49]
A. Villani, M. Lemire, M. Thabane et al., “Genetic risk factors for post-infectious irritable Bowel syndrome following a waterborne outbreak of gastroenteritis,” Gastroenterology, vol. 138, no. 4, pp. 1502–1513, 2010.
[50]
S. P. Dunlop, J. Hebden, E. Campbell et al., “Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes,” American Journal of Gastroenterology, vol. 101, no. 6, pp. 1288–1294, 2006.
[51]
T. Piche, G. Barbara, P. Aubert et al., “Impaired Intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators,” Gut, vol. 58, no. 2, pp. 196–201, 2009.
[52]
K. J. Lee, Y. B. Kim, J. H. Kim, H. C. Kwon, D. K. Kim, and S. W. Cho, “The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors,” Journal of Gastroenterology and Hepatology, vol. 23, no. 11, pp. 1689–1694, 2008.
[53]
K. A. Gwee, S. M. Collins, N. W. Read et al., “Increased rectal mucosal expression of interleukin 1β in recently acquired post-infectious irritable bowel syndrome,” Gut, vol. 52, no. 4, pp. 523–526, 2003.
[54]
K. J. Lee and J. Tack, “Altered intestinal microbiota in irritable bowel syndrome,” Neurogastroenterology and Motility, vol. 22, no. 5, pp. 493–498, 2010.
[55]
J. Chow, S. M. Lee, Y. Shen, A. Khosravi, and S. K. Mazmanian, “Host-bacterial symbiosis in health and disease,” Advances in Immunology, vol. 107, no. C, pp. 243–274, 2010.
[56]
I. Posserud, P. O. Stotzer, E. S. Bj？rnsson, H. Abrahamsson, and M. Simrén, “Small intestinal bacterial overgrowth in patients with irritable bowel syndrome,” Gut, vol. 56, no. 6, pp. 802–808, 2007.
[57]
A. Gasbarrini, E. C. Lauritano, M. Gabrielli et al., “Small intestinal bacterial overgrowth: diagnosis and treatment,” Digestive Diseases, vol. 25, no. 3, pp. 237–240, 2007.
[58]
U. C. Ghoshal, S. Kumar, M. Mehrotra, et al., “Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea,” Journal Neurogastroenterology and Motility, vol. 16, no. 1, pp. 40–46, 2010.
[59]
U. C. Ghoshal, “How to interpret hydrogen breath tests,” Journal of Neurogastroenterology and Motility, vol. 17, no. 3, pp. 312–317, 2011.
[60]
S. Chandra, U. Dutta, M. T. Noor et al., “Endoscopic jejunal biopsy culture: a simple and effective method to study jejunal microflora,” Indian Journal of Gastroenterology, pp. 1–5, 2011.
[61]
M. Pimentel, E. J. Chow, and H. C. Lin, “Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome: a double-blind, randomized, placebo-controlled study,” American Journal of Gastroenterology, vol. 98, no. 2, pp. 412–419, 2003.
[62]
U. C. Ghoshal, U. Ghoshal, K. Das, and A. Misra, “Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome, and its relationship with orocecal transit time,” Indian Journal of Gastroenterology, vol. 25, no. 1, pp. 6–10, 2006.
[63]
H. K. Berthold, P. Schober, C. Scheurlen et al., “Use of the lactose-[13C]ureide breath test for diagnosis of small bowel bacterial overgrowth: comparison to the glucose hydrogen breath test,” Journal of Gastroenterology, vol. 44, no. 9, pp. 944–951, 2009.
[64]
S. H. Kyoung, W. K. Hyoun, P. I. Jong et al., “Effect of probiotics on symptoms in Korean adults with irritable bowel syndrome,” Gut and Liver, vol. 3, no. 2, pp. 101–107, 2009.
[65]
S. J. Lewis, S. Franco, G. Young, and S. J. D. O'Keefe, “Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole,” Alimentary Pharmacology and Therapeutics, vol. 10, no. 4, pp. 557–561, 1996.
[66]
C. Williams and K. E. L. McColl, “Proton pump inhibitors and bacterial overgrowth,” Alimentary Pharmacology and Therapeutics, vol. 23, no. 1, pp. 3–10, 2006.
[67]
X. Fan and J. H. Sellin, “Small intestinal bacterial overgrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea,” Alimentary Pharmacology and Therapeutics, vol. 29, no. 10, pp. 1069–1077, 2009.
[68]
B. M. R. Spiegel, W. D. Chey, and L. Chang, “Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors?” American Journal of Gastroenterology, vol. 103, no. 12, pp. 2972–2976, 2008.
[69]
E. J. Schiffrin and S. Blum, “Interactions between the microbiota and the intestinal mucosa,” European Journal of Clinical Nutrition, vol. 56, supplement 3, pp. S60–S64, 2002.
[70]
T. Tanoue, Y. Umesaki, and K. Honda, “Immune responses to gut microbiota-commensals and pathogens,” Gut Microbes, vol. 1, no. 4, pp. 224–233, 2010.
[71]
S. Vaishnava, C. L. Behrendt, A. S. Ismail, L. Eckmann, and L. V. Hooper, “Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 52, pp. 20858–20863, 2008.
[72]
C. L. Ohland and W. K. MacNaughton, “Probiotic bacteria and intestinal epithelial barrier function,” American Journal of Physiology, Gastrointestinal and Liver Physiology, vol. 298, no. 6, pp. G807–G819, 2010.
[73]
R. C. Anderson, A. L. Cookson, W. C. McNabb et al., “Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation,” BMC Microbiology, vol. 10, article no. 316, 2010.
[74]
Z. H. Liu, T. Y. Shen, P. Zhang, Y. L. Ma, M. P. Moyer, and H. L. Qin, “Protective effects of Lactobacillus plantarum against epithelial barrier dysfunction of human colon cell line NCM460,” World Journal of Gastroenterology, vol. 16, no. 45, pp. 5759–5765, 2010.
[75]
Q. Zhou, W. W. Souba, C. M. Croce, and G. N. Verne, “MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome,” Gut, vol. 59, no. 6, pp. 775–784, 2010.
[76]
H. L. B. M. Klaasen, P. J. Van der Heijden, W. Stok et al., “Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice,” Infection and Immunity, vol. 61, no. 1, pp. 303–306, 1993.
[77]
S. K. Mazmanian, J. L. Round, and D. L. Kasper, “A microbial symbiosis factor prevents intestinal inflammatory disease,” Nature, vol. 453, no. 7195, pp. 620–625, 2008.
[78]
P. Veiga, C. A. Gallini, C. Beal et al., “Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 42, pp. 18132–18137, 2010.
[79]
V. Gaboriau-Routhiau, S. Rakotobe, E. Lécuyer et al., “The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses,” Immunity, vol. 31, no. 4, pp. 677–689, 2009.
[80]
T. Liebregts, B. Adam, C. Bredack et al., “Immune activation in patients With irritable Bowel syndrome,” Gastroenterology, vol. 132, no. 3, pp. 913–920, 2007.
[81]
L. Ohman, S. Isaksson, A. C. Lindmark et al., “T-cell activation in patients with irritable bowel syndrome,” American Journal of Gastroenterology, vol. 104, no. 5, pp. 1205–1212, 2009.
[82]
V. Z. Rocha and E. J. Folco, “Inflammatory concepts of obesity,” International Journal of Inflammation, vol. 2011, Article ID 529061, 14 pages, 2011.
[83]
N. Holmen, S. Isaksson, M. Simren, et al., “CD4+CD25+ regulatory T cells in irritable bowel syndrome patients,” Neurogastroenterology & Motility, vol. 19, no. 2, pp. 119–25, 2007.
[84]
H. C. Lin and K. Al-Khatib, “Immune activation and gut microbes in irritable bowel syndrome,” Gut and Liver, vol. 3, no. 1, pp. 14–19, 2009.
[85]
G. Barbara, “Toll-like receptor expression in irritable bowel syndrome: on the alert for a microbial threat,” American Journal of Gastroenterology, vol. 106, no. 2, pp. 337–339, 2011.
[86]
C. O'Mahony, P. Scully, D. O'Mahony et al., “Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation,” PLoS Pathogens, vol. 4, no. 8, Article ID e1000112, 2008.
[87]
O'Sullivan, Clayton, Breslin et al., “Increased mast cells in the irritable bowel syndrome,” Neurogastroenterology and Motility, vol. 12, no. 5, pp. 449–457, 2000.
[88]
B. E. Lacy, K. Weiser, and R. De Lee, “The treatment of irritable bowel syndrome,” Therapeutic Advances in Gastroenterology, vol. 2, no. 4, pp. 221–238, 2009.
[89]
W. D. Chey, M. Maneerattaporn, and R. Saad, “Pharmacologic and complementary and alternative medicine therapies for irritable bowel syndrome,” Gut and Liver, vol. 5, no. 3, pp. 253–266, 2011.
[90]
L. O'Mahony, J. Mccarthy, P. Kelly et al., “Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles,” Gastroenterology, vol. 128, no. 3, pp. 541–551, 2005.
[91]
T. Steer, H. Carpenter, K. Tuohy, and G. R. Gibson, “Perspectives on the role of the human gut microbiota and its modulation by pro- and prebiotics,” Nutrition Research Reviews, vol. 13, no. 2, pp. 229–254, 2000.
[92]
H. J. Kim, M. Camilleri, S. McKinzie et al., “A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 17, no. 7, pp. 895–904, 2003.
[93]
H. J. Kim, M. I. Vazquez Roque, M. Camilleri et al., “A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating,” Neurogastroenterology and Motility, vol. 17, no. 5, pp. 687–696, 2005.
[94]
G. A. Preidis and J. Versalovic, “Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era,” Gastroenterology, vol. 136, no. 6, pp. 2015–2031, 2009.
[95]
J. C. Y. Wu, “Complementary and alternative medicine modalities for the treatment of irritable bowel syndrome: facts or myths?” Gastroenterology and Hepatology, vol. 6, no. 11, pp. 705–711, 2010.
[96]
D. B. A. Silk, A. Davis, J. Vulevic, G. Tzortzis, and G. R. Gibson, “The effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 29, no. 5, pp. 508–518, 2009.
[97]
J. H. Cummings, G. T. Macfarlane, and H. N. Englyst, “Prebiotic digestion and fermentation,” American Journal of Clinical Nutrition, vol. 73, no. 2, supplement, pp. 415S–420S, 2001.
[98]
J. Schrezenmeir and M. De Vrese, “Probiotics, prebiotics, and synbiotics - Approaching a definition,” American Journal of Clinical Nutrition, vol. 73, no. 2, pp. 361S–364S, 2001.
[99]
S. Gupta, V. Kapoor, and B. Kapoor, “Itopride: a novel prokinetic agent,” Pharmacology, vol. 6, no. 2, pp. 106–108, 2004.
[100]
P. Paré, R. Bridges, M. C. Champion et al., “Recommendations on chronic constipation (including constipation associated with irrtable bowel syndrome) treatment,” Canadian Journal of Gastroenterology, vol. 21, supplement B, pp. 3B–22B, 2007.
[101]
D. Lesbros-Pantoflickova, P. Michetti, M. Fried, C. Beglinger, and A. L. Blum, “Meta-analysis: the treatment of irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 20, no. 11-12, pp. 1253–1269, 2004.
[102]
C. L. Frissora and B. D. Cash, “The role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 25, no. 11, pp. 1271–1281, 2007.
[103]
K. Tillisch and L. Chang, “Diagnosis and treatment of irritable bowel syndrome: state of the art,” Current Gastroenterology Reports, vol. 7, no. 4, pp. 249–256, 2005.
[104]
H. C. Lin, “Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome,” Journal of the American Medical Association, vol. 292, no. 7, pp. 852–858, 2004.
[105]
M. Pimentel, A. Lembo, W. D. Chey et al., “Rifaximin therapy for patients with irritable bowel syndrome without constipation,” New England Journal of Medicine, vol. 364, no. 1, pp. 22–32, 2011.
[106]
J. Maukonen, R. Satokari, J. M？tt？, H. S？derlund, T. Mattila-Sandholm, and M. Saarela, “Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria,” Journal of Medical Microbiology, vol. 55, no. 5, pp. 625–633, 2006.
[107]
A. P. M. Kerckhoffs, M. Samsom, M. E. van der Rest et al., “Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients,” World Journal of Gastroenterology, vol. 15, no. 23, pp. 2887–2892, 2009.
[108]
B. M. Sobieszczańska, J. Osek, D. Wa？ko-Czopnik, E. Dworniczek, and K. Jermakow, “Association of enteroaggregative Escherichia coli with irritable bowel syndrome,” Clinical Microbiology and Infection, vol. 13, no. 4, pp. 404–407, 2007.
[109]
A. Lyra, T. Rinttil？, J. Nikkil？ et al., “Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification,” World Journal of Gastroenterology, vol. 15, no. 47, pp. 5936–5945, 2009.
[110]
L. Krogius-Kurikka, A. Lyra, E. Malinen et al., “Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers,” BMC Gastroenterology, vol. 9, article no. 95, 2009.
[111]
J. M. Si, Y. C. Yu, Y. J. Fan, and S. J. Chen, “Intestinal microecology and quality of life in irritable bowel syndrome patients,” World Journal of Gastroenterology, vol. 10, no. 12, pp. 1802–1805, 2004.
[112]
C. Codling, L. O'Mahony, F. Shanahan, E. M. M. Quigley, and J. R. Marchesi, “A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome,” Digestive Diseases and Sciences, vol. 55, no. 2, pp. 392–397, 2010.
[113]
C. Tana, Y. Umesaki, A. Imaoka, T. Handa, M. Kanazawa, and S. Fukudo, “Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome,” Neurogastroenterology and Motility, vol. 22, no. 5, pp. 512–e115, 2010.
[114]
S.C. Ng, E. Lam, T. Y. Lam, et al., “Pyrosequencing alalysis reveals high level phylogenetic alterations in mucosal—associated intestinal microbiota of patients with irritable bowel syndrome,” Gut, vol. 60, 2011.
[115]
J. S. Park, J. H. Yu, H. C. Lim et al., “Usefulness of lactulose breath test for the prediction of small intestinal bacterial overgrowth in irritable bowel syndrome,” The Korean Journal of Gastroenterology, vol. 56, no. 4, pp. 242–248, 2010.
[116]
E. Scarpellini, V. Giorgio, M. Gabrielli et al., “Prevalence of small intestinal bacterial overgrowth in children with irritable Bowel syndrome: a case-control study,” Journal of Pediatrics, vol. 155, no. 3, pp. 416–420, 2009.
[117]
N. S. Mann and M. Limoges-Gonzales, “The prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome,” Hepato-Gastroenterology, vol. 56, no. 91-92, pp. 718–721, 2009.
[118]
G. Nucera, M. Gabrielli, A. Lupascu et al., “Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth,” Alimentary Pharmacology and Therapeutics, vol. 21, no. 11, pp. 1391–1395, 2005.
[119]
S. Sachdeva, A. K. Rawat, R. S. Reddy, and A. S. Puri, “Small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome: frequency and predictors,” Journal of Gastroenterology and Hepatology, vol. 26, supplement 3, pp. 135–138, 2011.
[120]
S. C. Reddymasu, S. Sostarich, and R. W. McCallum, “Small intestinal bacterial overgrowth in irritable bowel syndrome: are there any predictors?” BMC Gastroenterology, vol. 10, article no. 23, 2010.
[121]
A. C. Ford, B. M.R. Spiegel, N. J. Talley, and P. Moayyedi, “Small intestinal bacterial overgrowth in irritable Bowel syndrome: systematic review and meta-analysis,” Clinical Gastroenterology and Hepatology, vol. 7, no. 12, pp. 1279–1286, 2009.
[122]
A. Parodi, P. Dulbecco, E. Savarino et al., “Positive glucose breath testing is more prevalent in patients with IBS-like symptoms compared with controls of similar age and gender distribution,” Journal of Clinical Gastroenterology, vol. 43, no. 10, pp. 962–966, 2009.
[123]
S. V. Rana, S. K. Sinha, A. Sikander, D. K. Bhasin, and K. Singh, “Study of small intestinal bacterial overgrowth in North Indian patients with irritable bowel syndrome: a case control study,” Tropical Gastroenterology, vol. 29, no. 1, pp. 23–25, 2008.
[124]
M. Majewski and R. W. McCallum, “Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial,” Advances in medical sciences, vol. 52, pp. 139–142, 2007.
[125]
L. Cuoco and M. Salvagnini, “Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin,” Minerva Gastroenterologica e Dietologica, vol. 52, no. 1, pp. 89–95, 2006.
[126]
A. Lupascu, M. Gabrielli, E. C. Lauritano et al., “Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome,” Alimentary Pharmacology and Therapeutics, vol. 22, no. 11-12, pp. 1157–1160, 2005.
[127]
M. Grover, M. Kanazawa, O. S. Palsson et al., “Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress,” Neurogastroenterology and Motility, vol. 20, no. 9, pp. 998–1008, 2008.
