Irritable Bowel Syndrome antibiotic neomycin.50 Compared with placebo, patients receiving
neomycin had significant improvement of their symptoms. Also noteworthy was that all patients originally found to be methane producers had elimination of methane following treatment with neomycin. Although further investigation is warranted, methane gas may directly cause constipation symptoms. The ability to alter the concentration methanogenic flora may provide effective treatments for specific subgroups of IBS patients.
Probiotics
Probiotics are live micro-organisms that when ingested may alter the composition of the intestinal microbiome. Traditional treatments of IBS have been aimed at symptom control and have included antidiarrheal agents, fiber supplementation, and antispasmotics. In patients with more severe symptoms, 5-HT4 agonists, 5-HT3 antagonists, and antidepressants have been used to alter motility and hypersensitivity, two common hypotheses of IBS etiology.6
As evidence of the relationship between IBS
and altered intestinal flora has emerged, probiotics have become more commonly used.
Multiple mechanisms explaining the potential effectiveness of probiotics have been proposed. At the most basic level, probiotics are hypothesized to replenish reduced concentrations of enteric bacteria. For this reason, probiotics often consist of Bifidobacterium or Lactobacillus, both potentially decreased in IBS patients (see Table 1).14,15,17
Other studies
have used biomarkers to evaluate potential mechanisms. An immune modulating role of probiotics has been proposed based on the normalization of inflammatory cytokines following treatment.51
Our
understanding of probiotics appears to remain highly dependent on our understanding of existing enteric bacteria. As the roles of different bacterial species become more clearly recognized, our comprehension of probiotics and their mechanism will also improve.
Probiotics typically contain Lactobacillus, Bifidobacterium, or a combination of various bacteria. While multiple studies have attempted to determine the efficacy of probiotics in patients with IBS, differences in probiotic composition and dosing have limited researchers in making a definitive conclusion.52
In a systematic review performed by Brenner et
1. Boivin M, Socioeconomic impact of irritable bowel syndrome in Canada, Can J Gastroenterol, 2001;15(Suppl. B):8B–11B.
2. Bommelaer G, Poynard T, Le Pen C, et al., Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria, Gastroenterol Clin Biol, 2004;28(6–7 Pt 1):554–61.
3. Drossman DA, Morris CB, Schneck S, et al., International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit, J Clin Gastroenterol, 2009;43:541–50.
4. Hulisz D, The burden of illness of irritable bowel syndrome: current challenges and hope for the future, J Manag Care Pharm, 2004;10:299–309.
5. Berg RD, The indigenous gastrointestinal microflora, Trends Microbiol, 1996;4:430–5.
6. Mertz HR, Irritable bowel syndrome, N Engl J Med, 2003;349:2136–46.
7. Conly JM, Stein K, The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis, Prog Food Nutr Sci, 1992;16:307–43.
8. Macfarlane GT, Macfarlane S, Human colonic microbiota: ecology, physiology and metabolic potential of intestinal bacteria, Scand J Gastroenterol Suppl, 1997;222:3–9.
9. Bergogne-Berezin E, Treatment and prevention of antibiotic associated diarrhea, Int J Antimicrob Agents, 2000;16:521–6.
10. Spiller RC, Jenkins D, Thornley JP, et al., Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased
Summary
IBS continues to be a significant and challenging disorder faced by gastroenterologists and primary care physicians. The pathophysiology of IBS remains complex and its current diagnosis may actually encompass multiple distinct disease processes. The increased incidence of IBS following infectious gastroenteritis and potential association with SIBO and methanogenic flora suggests a relationship between altered bowel function and altered enteric bacteria. Differences between bacterial composition of healthy and IBS patients, in addition to evidence supporting the use of probiotics, further supports this relationship. Although numerous hypotheses for the development of IBS remain, the gut microbiome will likely provide new diagnostic tools and more effective treatments for patients with IBS. n
gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome, Gut, 2000;47:804–11.
11. Seksik P, Rigottier Gois L, Gramet G, et al., Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon, Gut, 2003;52:237–42.
12. Parkes GC, Brostoff J, Whelan K, et al., Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment, Am J Gastroenterol, 2008;103:1557–67.
13. Kerckhoffs AP, Samsom M, van der Rest ME, et al., Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients, World J Gastroenterol, 2009;15:2887–92.
14. Balsari A, Ceccarelli A, Dubini F, et al., The fecal microbial population in the irritable bowel syndrome, Microbiologica, 1982;5:185–94.
15. Matto J, Maunuksela L, Kajander K, et al., Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome—a longitudinal study in IBS and control subjects, FEMS Immunol Med Microbiol, 2005;43:213–22.
16. Maukonen J, Satokari R, Matto J, et al., Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria, J Med Microbiol, 2006;55(Pt 5):625–33.
17. Malinen E, Rinttilä T, Kajander K, et al., Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR, Am J Gastroenterol, 2005;100:373–82.
18. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al., An evidence- based position statement on the management of irritable bowel syndrome, Am J Gastroenterol, 2009;104(Suppl. 1):S1–35.
19. Thabane M, Marshall JK, Post-infectious irritable bowel syndrome, World J Gastroenterol, 2009;15:3591–6.
20. Thabane M, Kottachchi DT, Marshall JK, Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome, Aliment Pharmacol Ther, 2007;26:535–44.
21. Halvorson HA, Schlett CD, Riddle MS, Postinfectious irritable bowel syndrome—a meta-analysis, Am J Gastroenterol, 2006;101:1894–9, quiz 1942.
22. Dunlop SP, Jenkins D, Spiller RC, Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome, Am J Gastroenterol, 2003;98:1578–83.
23. Neal KR, Barker L, Spiller RC, Prognosis in post-infective irritable bowel syndrome: a six year follow up study, Gut, 2002;51:410–3.
24. Spiller RC, Role of infection in irritable bowel syndrome, J Gastroenterol, 2007;42(Suppl. 17):41–7.
25. Marshall JK, Thabane M, Borgaonkar MR, James C, Postinfectious irritable bowel syndrome after a food-borne outbreak of acute gastroenteritis attributed to a viral pathogen, Clin Gastroenterol Hepatol, 2007;5:457–60.
26. Soyturk M, Akpinar H, Gurler O, et al., Irritable bowel syndrome in persons who acquired trichinellosis, Am J Gastroenterol, 2007;102:1064–9.
al., 16 randomized controlled trials (RCTs) using a variety of probiotics— including species of Bifidobacterium and Lactobacillus—were evaluated.53
Brenner et al. concluded that 11 of 16 studies had
suboptimal study designs and only B. infantis 35624 to be efficacious in the treatment of IBS. The authors did, however, comment that even those studies supporting B. infantis 35624 lacked evidence of long-term symptomatic improvement. In another systematic review by Moayyedi et al., 19 RCTs were reviewed.54
Evaluating studies using dichotomous data,
found probiotics to be significantly better than placebo at reducing IBS symptoms. No difference between the effectiveness of different species of bacteria was found. When evaluating studies using continuous data, however, only Bifidobacteria was found to be effective in the treatment of IBS symptoms.
The ACG’s latest guidelines for the management of IBS specifically address probiotics.18
Its recommendation is based on the systematic
review performed by Moayyedi et al. Probiotics are given a 2C recommendation based on low-quality evidence and uncertainty of benefit versus risk for treatment. The ACG guidelines state that combinations of bacteria or Bifidobacteria alone may be effective in treating IBS. Although probiotics are likely to provide symptomatic relief in some patients with IBS, further studies are warranted to better define the efficacy of different micro-organisms, appropriate dosing, and duration of treatment.
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