# Bacterial flora in irritable bowel syndrome: role in pathophysiology, implications fo



## eric (Jul 8, 1999)

FYIBacterial flora in irritable bowel syndrome: role in pathophysiology, implications for management.Quigley EM.Alimentary Pharmabiotic Center, University College Cork, Cork, IRELAND.Irritable bowel syndrome (IBS) may, in part at least, result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa which, in turn, leads to immune activation in the colonic mucosa. Some propose a role for bacterial overgrowth as a common causative factor in the pathogenesis of symptoms in IBS; other evidence points to more subtle qualitative changes in the colonic flora; *both hypotheses remain to be confirmed but the likelihood that bacterial overgrowth will prove to be a major factor in IBS now seems remote.* Nevertheless, short-term therapy with either antibiotics or probiotics does seem to reduce symptoms among IBS patients. It seems most likely that the benefits of antibiotic therapy are mediated through subtle and, perhaps, localized, quantitative and/or qualitative changes in the colonic flora. How probiotics exert their effects remain to be defined but an anti-inflammatory effect seems likely. While this approach to the management of IBS is in its infancy, it is evident that manipulation of the flora, whether through the administration of antibiotics or probiotics, deserves further attention in IBS.PMID: 17261128 There is an excellent and BALANCED article in the new IFFGD "Digestive Health Matters.""Gut Bacteria and Irritable Bowel Syndrome By: Eamonn, M. M. Quigley M.D., Alimentary Pharmabiotic Centre, University College Cork, Cork, IrelandBacteria are present in the normal gut (intestines) and in large numbers the lower parts of the intestine. These "normal" bacteria have important functions in life. A variety of factors may disturb the mutually beneficial relationship between the flora and its host, and disease may result. The possibility that gut bacteria could have a role in irritable bowel syndrome (IBS) may surprise some; there is indeed, now quite substantial evidence to support the idea that disturbances in the bacteria that populate the intestine may have a role in at least some patients with IBS. This article presents a discussion of the possible role of bacteria in IBS and various treatment approaches."http://www.aboutibs.org/Publications/currentParticipate.htmlYou can email them or call there toll free number to inquire getting this issue. It also has other really good articles in it as well.A lot of work went into these to articles to make them as easy and understandable to read as possble.


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## eric (Jul 8, 1999)

This is a study done In this study they used rifaximin on a group of patients with bloating and flatulence WHO DID NOT HAVE EVIDENCE OF SIBO. So anoher "explanation for a role of antibiotics in IBS, is a suppresion of certain species of bateria in the colon, and especially those bacteria that are prone to produce gas and other substances through fermentation, could also expalain these responces."A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence.Am J Gastroenterol. 2006; 101(2):326-33 (ISSN: 0002-9270)Sharara AI ; Aoun E ; Abdul-Baki H ; Mounzer R ; Sidani S ; Elhajj IGastroenterology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03). This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p < 0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3 (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.PreMedline Identifier: 16454838


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## eric (Jul 8, 1999)

FYIGastroenterology, February 2006 Journal Scan FromThe American Journal of GastroenterologyFebruary 2006 ( Volume 101, Number 2 ) A Randomized Double-Blind Placebo-Controlled Trial of Rifaximin in Patients With Abdominal Bloating and FlatulenceSharara AI, Aoun E, Abdu-Baki H, et al The American Journal of Gastroenterology. 2006;101(2):326-323Summary: Population-based studies performed in the United States have revealed a relatively high prevalence (16%-26%) of abdominal bloating.[1] Rectal flatus is a very common symptom in these patients as well. This syndrome of altered bowel habits and abdominal pain has typified the diagnosis of irritable bowel syndrome (IBS). Although the pathophysiology of this syndrome is not clearly defined, there has been some evidence to suggest that bacterial overgrowth may play a role in symptom development. This alteration in gut microflora may contribute to the symptoms -- in particular, with regard to gaseous distention, bloating, and rectal flatus. If bacteria have a putative role in the pathophysiology of this condition, it has been suggested that antibiotic therapy may be therapeutic. The antibiotic rifaximin is a rifamycine derivative, with particular effectiveness against enteric bacteria (including anaerobes). As a nonabsorbable antibiotic, it has no significant systemic side effects.Sharara and colleagues conducted a randomized, prospective placebo-controlled trial involving 124 patients who reported more than 12 weeks of bloating and/or excessive flatulence associated with chronic abdominal pain, abnormal bowel function, or obstipation. Extensive chart review allowed for exclusion of significant disease. All patients underwent a lactulose hydrogen breath test (LHBT) before randomization to either rifaximin (two 200-mg tablets twice daily for 10 days) or look-alike placebo. The treatment groups were well balanced and all patients suffered from gas-related symptoms such as bloating and/or excessive rectal flatus for an extended duration (range in symptoms, 7 months to 6 years). There were no differences between the 2 study groups relative to baseline LHBT.The primary study objective was patient-reported global improvement. There was a significant difference in global symptom relief among those patients who received rifaximin vs those who received placebo (41.3% vs 22.9%; P = .02). These differences were also significant for a subgroup analysis of patients who met the Rome II criteria for IBS. In patients who did not meet the criteria for the IBS diagnosis, the response difference between groups was not statistically significant (42.3% vs 28.6%; P = NS). Although all patients had normal LHBT, paired testing showed a decrease after 10 days of rifaximin treatment; this difference was not statistically significant. However, a subgroup analysis did demonstrate a significant drop in LHBT for responders, with a decrease in bloating-specific and overall symptom scores (P = .01).Commentary: Rifaximin has been used for nearly 20 years in Europe and the extended safety profile has been excellent. This drug has many features that suggest that it would represent a good adjunct for the treatment of a variety of diseases. This agent is nonabsorbable, nonsystemic, and has a very low bacterial resistance rate. Stool cultures were not conducted as part of this study, but they would be warranted, particularly if this drug were to be used for long-term or repeated cyclic intervals. Additionally, recent work has also focused on the use of this agent in the management of hepatic encephalopathy and inflammatory bowel disease.These study results demonstrate a significant relief effect with rifaximin for the management of symptoms of abdominal bloating, distention, and rectal flatus. *It is interesting that all subjects had normal LHBTs, suggesting that the benefit seen with rifaximin was not due to antibiotic treatment of small intestinal overgrowth. More likely, the outcome represents an antimicrobial effect on pathogenic organisms in the colon that cause the formation of excessive gas, presumably via excessive fermentation of complex carbohydrates.* There is no extended follow-up of the patients who participated in this study, and it will be of interest to observe the relapse data as well as the effects of re-treatment -- either with extended or intermittent cycles of therapy. Clearly, more investigation is warranted in this area, but the response demonstrated in this study offers a potentially new and promising treatment approach to a common and vexing clinical problem.ReferenceSandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci. 2000;45:1166-1171.


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## eric (Jul 8, 1999)

FYIIs Rifaximin More Effective Than Placebo in Reducing Symptoms in Adults With IBS?Pimentel M, Park S, Mirocha J, et al. 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.There has been a resurgence of interest recently in the area of small intestinal bacterial overgrowth (SIBO). Several studies conducted by Pimentel and colleagues have shown a high prevalence of SIBO in IBS patients (reviewed in reference [5]). As a natural consequence of this finding, antibiotics are now being evaluated as possible options in the treatment of IBS. One antibiotic in particular, rifaximin, has generated significant interest because it has minimal systemic absorption (< 0.4%). In the current study by Pimentel and colleagues,[6] men and women between the ages of 18 and 65 years and who met Rome I criteria for IBS were eligible for inclusion. Patients completed a 7-day stool diary based on the Bristol stool scale, and were then randomized to receive either placebo or rifaximin (400 mg) orally 3 times per day for 10 days. Patients then completed another 7-day stool diary and during the follow-up phase completed a weekly self-administered questionnaire for an additional 9 weeks (10 weeks of follow-up, total). The primary endpoint assessed was global improvement (percentage) in IBS across the 10 weeks. The study involved 87 patients from 2 separate medical centers who were randomized and evaluated using intention-to-treat analysis. The groups were similar with regard to age, weight, and sex; however, pain severity was higher in the rifaximin group. Patients randomized to rifaximin demonstrated an overall improvement in symptoms during the 10-week period compared with placebo (P = .020). Secondary analysis using a visual analogue scale demonstrated that bloating was better (lower bloating score) in the rifaximin group compared with placebo (P = .01). *Visual analogue scores for abdominal pain, diarrhea, and constipation were not different between the 2 treatment groups.*This study is interesting because it is the largest study performed to date to assess the efficacy of rifaximin in the treatment of IBS. However, the findings need to be interpreted with caution for a number of reasons. First, the rifaximin group had a higher level of pain at baseline, and thus would be more likely to show improvement using the outcomes specified by the research group. Second, there was a dramatic difference in patient recruitment between the 2 centers (84 vs 3), which raises the issue of eligibility and recruitment bias. Third, the endpoint for analysis was the percentage improvement over the trial period. This is not the endpoint typically used in IBS trials, and the study authors did not state a priori what was considered a treatment responder. *Fourth, these results suggest that bloating may be the symptom that responds best to treatment with rifaximin.* However, the study authors did not report the results of hydrogen breath tests that were performed in all of the subjects. Therefore, while certainly thought-provoking, this study raises many more questions than it answers. *For example, a number of other research groups have yet to replicate the high prevalence rates of SIBO in IBS patients reported by these investigators.* *In addition, many clinicians are now reporting that patients need recurrent treatment with rifaximin to alleviate symptoms of bloating, which can be costly.* It is clear that additional research is warranted to better define the prevalence and role of SIBO in the pathogenesis and treatment of IBS."http://www.medscape.com/viewarticle/548916_4I think this"many clinicians are now reporting that patients need recurrent treatment with rifaximin to alleviate symptoms of bloating, which can be costly" is more then just a cost issue, that there is also the long term taking antibiotics to think about as well.


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## eric (Jul 8, 1999)

FYICurr Opin Gastroenterol. 2007 Mar;23(2):127-33.Small intestinal motility.Bratten JR, Jones MP. Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.PURPOSE OF REVIEW: The aim of this article is to review recently published studies presenting novel and relevant information on small intestinal motility. RECENT FINDINGS: The reviewed studies covered a variety of topics with several themes emerging. The presentation and causes of chronic intestinal dysmotility continue to expand. Evidence continues to accrue that at least a subset of patients with severe colonic inertia may have a more diffuse motility disorder highlighting the need for careful assessment prior to embarking on surgery for refractory constipation. While interest in bacterial overgrowth in irritable bowel syndrome continues, *the utility and specificity of lactulose hydrogen breath testing is yet again being called into question.* Methane appears to slow intestinal transit and constipation appears more common among methane-positive patients. *The association is presently only correlative* and further study is needed. SUMMARY: Small intestinal motility remains an understudied area. Recent publications provide additional new information related to physiology and pathophysiology of small bowel motility. These findings should be of interest to clinician and investigator alike.PMID: 17268240 andDig Liver Dis. 2007 Jan 29; Epub ahead of print New insights into the pathogenesis and pathophysiology of irritable bowel syndrome.Ohman L, Simren M. Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.The pathogenesis and pathophysiology of irritable bowel syndrome is complex and still incompletely known. Potential pathogenetic factors include genes, infectious events, psychological symptoms and other loosely defined environmental factors. Both alterations at the central and peripheral level are thought to contribute to the symptoms of irritable bowel syndrome, including psychosocial factors, abnormal gastrointestinal motility and secretion, and visceral hypersensitivity. *Today irritable bowel syndrome is viewed upon as a disorder of dysregulation of the so-called brain-gut axis*, involving abnormal function in the enteric, autonomic and/or central nervous systems, with peripheral abnormalities probably dominating in some patients and disturbed central processing of signals from the periphery in others. Lines of evidence also suggest that inflammation within the gastrointestinal tract may be of great importance in at least subgroups of irritable bowel syndrome patients. To conclude, a complex picture of the pathogenesis and pathophysiology of irritable bowel syndrome is emerging, with interactions between several different alterations resulting in the divergent symptom pattern in these patients.PMID: 17267314


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## Rick (never give up) (Oct 7, 2005)

All I have to say is that I think this goes along with what I've been thinking lately.I've been talking GSE for a couple of weeks now, and, as well as with other things I've taken before, anythng that tends to lower bowel flora activity somehow seems to help with my IBS symptoms.So perhaps it is not SIBO after all, at least not for certain. I feel from my own experience that Bowel Flora activity is related to IBS symptoms, but may not be what keeps the chronic condition going, nevertheless it helps to keep it in check, at least for me.


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## cynthia (May 9, 2006)

Rick,I don't understand why you think that, after having somewhat positive results with GSE, your problem may not be SIBO. GSE has antibiotic properties so I would think that the fact that you're doing better while taking it would mean it is killing off the bacteria. What am I missing here?Cynthia


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## Rick (never give up) (Oct 7, 2005)

Hi Cynthia,The reason I think it's not SIBO is because I did the Vivonex diet a couple of months ago and it didn't alleviate my overall IBS. Before that I had the breath test which suggested SIBO, after that I had another breath test and this time the test indicated that SIBO was erradicated (at least I did't get the 2 peaks I got in the first one). However, I can pretty much tell you that my IBS is not over, except for the bloating which was considerably reduced after the Vivonex and and still remains that way.Hence, I can only think that bacteria play a role but at least in my case SIBO was not the cause.


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## Rick (never give up) (Oct 7, 2005)

There's something else I want to add as well.Personal experience is as important as good research. So, besides whatever all the research articles may say about SIBO, I think, that when I say bacteria is somehow involved I really mean, from my personal experience with IBS, that reducing bacterial population reduces many of the things that my gut is overreactive to, like gas for instance.So, why can't it be that taking GSE just lowers my total bacterial population, which in turn may reduce gas, reducing pressure and ending in my viceral hipersensitivity being protected from a lot of those natural stimulus that normal people will not complain about, but will in my case bring about IBS pain, bloating, etc.Is bacteria the cause or just a supporting role actor?What is definetly true right now is that no one can answer that question yet, either to prove it nor to deny it.


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## eric (Jul 8, 1999)

FYIRick, I highly recomened reading this article whcih you can get from the IFFGD"Gut Bacteria and Irritable Bowel Syndrome By: Eamonn, M. M. Quigley M.D., Alimentary Pharmabiotic Centre, University College Cork, Cork, IrelandBacteria are present in the normal gut (intestines) and in large numbers the lower parts of the intestine. These "normal" bacteria have important functions in life. A variety of factors may disturb the mutually beneficial relationship between the flora and its host, and disease may result. The possibility that gut bacteria could have a role in irritable bowel syndrome (IBS) may surprise some; there is indeed, now quite substantial evidence to support the idea that disturbances in the bacteria that populate the intestine may have a role in at least some patients with IBS. This article presents a discussion of the possible role of bacteria in IBS and various treatment approaches."Do bacteria play a role in IBS?The possibility that gut bacteria could have a role Irritable Bowel Syndrome (IBS) may surprize some; there is indeed, now quite substantial evidence to support the idea that distrubances in the bacteria that populate the intestines may have a role in at least some patients with IBS. What is this evidence? It can be summarized as follows:1. surveys which found that antibiotic use, well known to distrub flora, may predispose individuals to IBS.2. The observation that some individuals may develop IBS suddenly, and for the first time, following an episode of stomach or intestinal infection (gatroenteritis) caused by a bacterial infection.3. recent evidence that a very low level of inflammation may be present in the bowel wall of some IBS patients, a degree of inflammation that could well have resulted from abnormal interactions with bacteria in the gut.4. The Suggestion that IBS maybe Associated with the abnormal presents, , in the small intestines, of types and numbers; a condition termed small bacterial overgrowth (SIBO)>5. Accumaliting evidence to indicate that altering the bacteria in the gut, by antibiotics or probiotics, may improve symptoms in IBS.For some time, various studies have suggested the presence of changes in the kind of colonic flora in IBS patients. The most consistent finding is a relative decrease in the population of one species of 'good' bacteria, bifidobacteria.However, the methods employed in these studies have been subject to question and other studies have not always reproduced these finding. Nevertheless, these changes in the flora, maybe primary or secondary, could lead to the increase of bacterial species that produce more gas and other products of their metabolism. These could CONTRIBUTE to symptoms such as gas, bloating and diarrhea.""We still don't know the exact role bacteria has in IBS. More research is needed."http://www.aboutibs.org/Publications/currentParticipate.htmlI highly encourage others to read the read of this excellent article.


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## cynthia (May 9, 2006)

Rick,When you say the vivonex only partially alleviated your symptoms, what exactly did it do? What symptoms improved and what symptoms did not?Cynthia


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## Rick (never give up) (Oct 7, 2005)

I took Vivonex for 2 full weeks. After that I waited a month cause that is the recommended time to assess how the protocol worked.After that, and still currently, my IBS is the same. I have alternating pain, sometimes diahrea and/or constipation, etc.The only thing that improved was the bloating. Before I used to be very bloated all the time. Now I feel bloated only after eating too many carbs, and it usually goes away if I control myself.With GSE, I've noticed that I tend to be more constipated and never with diahrea. But I've only taken it for 4 weeks, and in a moderate dosage.You may read my Vivonex diary on this same section. It's from October last year or so.


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