Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms： Experience with Rifaximin

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.
METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.
RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS.
CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.     

Hydrogen breath test for the diagnosis of lactose intolerance, is the routine sugar load the best one？

AIM： To evaluate the prevalence of lactose intolerance （LI） following a load of 12.5 g in patients diagnosed as high-grade malabsorbers using the hydrogen breath test （HBT）-25. METHODS： Ninety patients showing high-grade malabsorption at HBT-25 were submitted to a second HBT with a lactose load of 12.5 g. Peak hydrogen production, area under the curve of hydrogen excretion and occurrence of symptoms were recorded. RESULTS： Only 16 patients （17.77%） with positive HBT-25 proved positive at HBT-12.5. Hydrogen production was lower as compared to HBT-25 （peak value 21.55 parts per million （ppm） ± 29.54 SD vs 99.43 ppm ± 40.01 SD; P 〈 0.001）. Symptoms were present in only 13 patients. The absence of symptoms during the high-dose test has a high negative predictive value （0.84） for a negative low-dose test. The presence of symptoms during the first test was not useful for predicting a positive low-dose test （positive predictive value 0.06-0.31）. CONCLUSION： Most patients with a positive HBT-25 normally absorb a lower dose of lactose and a strict lactose restriction on the basis of a ＂standard＂ HBT is, in most instances, unnecessary. Thus, the 25 g lactose tolerance test should probably be substituted by the 12.5 g test in the diagnosis of LI, and in providing dietary guidelines to patients with suspected lactose malabsorption/intolerance.     

Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome

AIM： To determine whether Lactobacillus casei strain Shirota （Yakult） can alter small intestinal bacterial overgrowth （SIBO）, as tested by the lactulose breath test, and whether this is associated with changes in symptoms in irritable bowel syndrome （IBS）. METHODS： 18 patients with IBS （Rome Ⅱ criteria）, who showed an early rise in breath hydrogen with lactulose （ERBHAL）, consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period. Symptoms were recorded daily using a 10 cm visual analogue scale. RESULTS： 14 patients completed the study, 9 （64%） had reversal of ERBHAL, with the median time of first rise in breath hydrogen increasing from 45 to 75 min （P = 0.03）. There was no significant improvement in the symptom score with probiotic therapy, except for wind （P = 0.04）. Patients commencing with at least moderate symptoms and who no longer had ERBHAL at the end of treatment, showed improvement in the overall symptoms scores [median final score 5.3 （IQR 3.9-5.9）, 55% reduction; n = 6] to a greater extent than those who had had persisting ERBHAL [final score 6.9 （5.0-7.0）, 12% reduction; n = 5; P = 0.18]. CONCLUSION： Yakult is effective in altering fermentation patterns in the small bowel, consistent with reducing SIBO. The loss of ERBHAL was associated with reduced symptoms. The true interpretation of these findings awaits a randornised, controlled trial.     

Breath tests and irritable bowel syndrome

Breath tests are non-invasive tests and can detect H2and CH4 gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath.These tests are used in the diagnosis of carbohydrate malabsorption,small intestinal bacterial overgrowth,and for measuring the orocecal transit time.Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome(IBS)-type symptoms such as diarrhea and/or constipation,bloating,excess flatulence,headaches and lack of energy.Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life.It may reflect dietary imbalance,such as excess fiber intake,or may be a manifestation of IBS.However,bloating may also represent small intestinal bacterial overgrowth.Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H2 breath testing to determine the presence or absence of bacterial overgrowth.If bacterial overgrowth is identified,patients are typically treated with antibiotics.Evaluation of IBS generally includes testing of other disorders that cause similar symptoms.Carbohydrate malabsorption(lactose,fructose,sorbitol)can cause abdominal fullness,bloating,nausea,abdominal pain,flatulence,and diarrhea,which are similar to the symptoms of IBS.However,it is unclear if these digestive disorders contribute to or cause the symptoms of IBS.Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS.Thus,diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients.     

Evaluation of thermal water in patients with functional dyspepsia and irritable bowel syndrome accompanying constipation

AIM: To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowe syndrome (IBS) accompanying predominant constipation. METHODS: A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d. A year later patients were re-evaluated at the same centre and received another cycle of thermal therapy. A questionnare to collect personal data on social and occupational status, family and pathological case history, life style, clinical records, utilisation of welfare and health structure and devices was administered to each patient at basal time and one year after each thermal treatment. Sixty patients with functional dyspepsia and 20 with IBS and 80 healthy controls received an evaluation of gastric output and oro-cecal transit time by breath test analysis. Breath test was performed at basal time and after water supplementaton therapies. Gastrointestinal symptoms were evaluated at the same time points. Breath samples were analyzed with a mass spectometer and a gascromatograph. Results were expressed as T1/2 and T-lag for octanoic acid breath test and as oro-cecal transit time for lactulose breath test. RESULTS: A significant reduction of prevalence of symptoms was observed at the end of the first and second cycles of thermal therapy in dyspeptic and IBS patients. The analysis of variance showed a real and persistant improvement of symptoms in all patients. After water supplementation for 3 wk a reduction of gastric output was observed in 49 (87.5%) of 56 dyspeptic patients. Both T1/2 and T-lag were significantly reduced after the therapy compared to basal values [91±12 (T1/2) and 53±11(T-lag), Tables 1 and 2] with results of octanoic acid breath test similar to healthy subjects. After water supplementation for 3 wk oro-cecal transit time was shorter than that at the beginning of the study. CONCLUSION: Mineral water supplementation treatment for functional dyspepsia or conspipation accompanying IBS can improve gastric acid output and intestinal transit time.     

Role of Helicobacter pylori in functional dyspepsia

The aetiology of dyspepsia is unknown in the majority of patients. Helicobacter pylori (H pylori) is the cause in a subset of patients. A non invasive test to assess the presence of H pylori is recommended in the management of patients under the age of 50 presenting to a family practitioner with dyspepsia. A urea breath test or a stool antigen test are the most reliable non invasive tests. Eradication of H pylori will reduce the risk to the patient with dyspepsia of developing a peptic ulcer, reduce the complication rate if prescribed nonsteroid anti-inflammatory drugs and later reduce the risk of gastric cancer. The recommended treatment for non ulcer dyspepsia associated with a H pylori infection should be a 10-d course of treatment with a PPI and two antibiotics. Treatment efficacy should be assessed four weeks after completing treatment with a urea breath test or a stool antigen test.     

14C-urea breath test in patients undergoing anti-tuberculosis therapy

AIM: Urea breath test (UBT) is a non-invasive diagnostic test for detecting the presence of Helicobacterpylori(H pylori). In this study we evaluated the effect of anti-tuberculosis therapy on the results of 14C-UBT. METHODS: Patients, with the diagnosis of tuberculosis (TB) who had a positive UBT at the point of starting anti-TB therapy, were included. None had a history of peptic ulcer disease or had taken antibiotics, bismuth compounds and/or PPI in the previous month. 14C-UBT was repeated at the end of the second month and the end of treatment period and one month after completion of treatment course. RESULTS: Thirty-five patients (23 males) were enrolled. 14C-UBT was negative in all 35 patients (100%) at the end of the second month and remained negative in 30 cases (85.7%) at the end of the treatment course. One month after completion of treatment course, UBT remained negative in 13 patients (37.1%). CONCLUSION: Our report underscores the need for caution while interpreting urea breath test results in patients undergoing anti-TB therapy. Furthermore, the combination of drugs used in this study resulted in H pylori eradication in a minority of patients.     

Relationship of functional gastrointestinal disorders and psychiatric disorders： Implications for treatment

This article revisits the links between psychopathology and functional gastrointestinal disorders such as irritable bowel syndrome （IBS）, discusses the rational use of antidepressants as well as non-pharmacological approaches to the management of IBS, and suggests guidelines for the treatment of IBS based on an interdisciplinary perspective from the present state of knowledge. Relevant published literature on psychiatric disorders, especially somatization disorder, in the context of [BS, and literature providing direction for management is reviewed, and new directions are provided from findings in the literature. IBS is a heterogeneous syndrome with various potential mechanisms responsible for its clinical presentations. IBS is typically complicated with psychiatric issues, unexplained symptoms, and functional syndromes in other organ systems. Most IBS patients have multiple complaints without demonstrated cause, and that these symptoms can involve systems other than the intestine, e.g. bones and joints （fibromyalgia, temporomandibular joint syndrome）, heart （non-cardiac chest pain）, vascular （post-menopausal syndrome）, and brain （anxiety, depression）. Host IBS patients do not have psychiatric illness per se, but a range of psychoform （psychological complaints in the absence of psychiatric disorder） symptoms that accompany their somatoform （physical symptoms in the absence of medical disorder） complaints. It is not correct to label IBS patients as psychiatric patients （except those more difficult patients with true somatization disorder）. One mode of treatment is unlikely to be universally effective or to resolve most symptoms. The techniques of psychotherapy or cognitive-behavioral therapy can allow IBS patients to cope more readily with their illness. Specific episodes of depressive or anxiety disorders can be managed as appropriate for those conditions. Medications designed to improve anxiety or depression are not uniformly useful for psychiatric complaints in IBS, because the p     

Irritable bowel syndrome: physicians' awareness and patients' experience

AIM: To study if and how physicians use the irritable bowel syndrome (IBS) diagnostic criteria and to assess treatment strategies in IBS patients. METHODS: A questionnaire was sent to 191 physicians regarding IBS criteria, diagnostic methods and treatment. Furthermore, 94 patients who were diagnosed with IBS underwent telephone interview. RESULTS: A total of 80/191 (41.9%) physicians responded to the survey. Overall, 13 patients were diag-nosed monthly with IBS by specialists in gastroenterology (SGs) and 2.5 patients by general practitioners (GPs). All the SGs knew of the criteria to diagnose IBS, as did 46/70 (65.7%) GPs. Seventy-nine percent used the patient’s history, 38% used a physical examination, and 38% exclusion of other diseases to diagnose IBS. Only 18/80 (22.5%) physicians used specific IBS criteria. Of the patients interviewed, 59/94 (62.8%) knew they had experienced IBS. Two out of five patients knew IBS and had seen a physician because of IBS symptoms. Half of those received a diagnosis of IBS. A total of 13% were satisfied with treatment. IBS affected daily activities in 43% of cases. CONCLUSION: Half of the patients with IBS who consulted a physician received a diagnosis. Awareness and knowledge of diagnostic criteria for IBS differ between SGs and GPs.     

Complementary and alternative medicines in irritable bowel syndrome: An integrative view

Irritable bowel syndrome(IBS)is a common gastrointestinal disorder with a high incidence in the general population.The diagnosis of IBS is mainly based on exclusion of other intestinal conditions through the absence of inflammatory markers and specific antigens.The current pharmacological treatment approaches available focus on reducing symptom severity while often limiting quality of life because of significant side effects.This has led to an effectiveness gap for IBS patients that seek further relief to increase their quality of life.Complementary and alternative medicines(CAM)have been associated with a higher degree of symptom management and quality of life in IBS patients.Over the past decade,a number of important clinical trials have shown that specific herbal therapies(peppermint oil and Iberogast?),hypnotherapy,cognitive behavior therapy,acupuncture,and yoga present with improved treatment outcomes in IBS patients.We propose an integrative approach to treating the diverse symptoms of IBS by combining the benefits of and need for pharmacotherapy with known CAM therapies to provide IBS patients with the best treatment outcome achievable.Initial steps in this direction are already being considered with an increasing number of practitioners recommending CAM therapies to their patients if pharmacotherapy alone does not alleviate symptoms sufficiently.     

The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin

The findings of the lactulose breath test in irritable bowel syndrome patients have been used to suggest that most patients have small intestinal bacterial overgrowth (SIBO), and this association has spawned the widespread use of antibiotics in IBS. The study by Bratten and colleagues demonstrates that this test does not discriminate between IBS patients and healthy controls when criteria from recent clinical IBS studies are applied. When the findings from this large study are combined with previous smaller studies, they challenge the hypothesis that SIBO underlies the symptoms of IBS and undermine the current rationale for the use of antibiotics in IBS.     

Restless Legs Syndrome in Patients with Irritable Bowel Syndrome: Response to Small Intestinal Bacterial Overgrowth Therapy

Background Small intestinal bacterial overgrowth (SIBO) occurs in irritable bowel syndrome (IBS) and fibromyalgia. Since restless legs syndrome (RLS) occurs with fibromyalgia, a link between IBS, SIBO, and RLS was studied. Methods BS patients with abnormal lactulose breath tests received rifaximin 1,200 mg day⁻¹ for 10 days, followed by tegaserod 3 mg, long-term, and 1 month of zinc 220 mg day⁻¹ and once-daily probiotic (N = 11) or rifaximin monotherapy (N = 2). IBS symptom improvement was assessed after rifaximin. RLS symptoms, IBS symptoms, and overall IBS global improvement were assessed at last posttreatment visit: 8/10 patients were followed long-term (mean, 139 days; range, 54–450 days). Results Ten of 13 patients exhibited ≥80% improvement from baseline in RLS symptoms. Five maintained complete resolution of RLS symptoms. Global gastrointestinal symptom improvement was great (n = 6), moderate (n = 5), or mild (n = 2). Conclusion This study suggests that SIBO associated with IBS may be a factor in some RLS patients and SIBO therapy provides long-term RLS improvement.     

Bacterial concepts in irritable bowel syndrome

An overlap of symptoms in irritable bowel syndrome (IBS) exists across subtype groups. Symptoms include intestinal gas, diarrhea, dyspepsia, bloating, abdominal pain, and constipation. The unifying symptom may be excessive intestinal gas as a by-product of intestinal microbial fermentation. Abnormal fermentation of food takes place when gut microbes expand proximally into the small intestine instead of being confined predominantly to the colon. Such proximal expansion of indigenous gut microbes or small intestinal bacterial overgrowth (SIBO) may lead to activation of host mucosal immunity and an increase in intestinal permeability to result in flu-like extra-intestinal symptoms that accompany the classic IBS symptoms of altered bowels. The presence of methane on lactulose breath testing is associated with constipation-predominant IBS. Antibiotic therapy may be appropriate to treat underlying SIBO in IBS patients. Seventy-five percent improvement of IBS symptoms was reported in a double-blind, placebo-controlled study once antibiotics succeeded in treating bacterial overgrowth. Once a good clinical response and normalization of the lactulose breath test are achieved, a prokinetic agent may be used to stimulate phase III of interdigestive motility to delay relapse of bacterial overgrowth.     

Is irritable bowel syndrome an infectious disease?

Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.     

Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test,suggesting bacterial overgrowth

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case–control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 ± 0.8 in IBS subjects and 2.2 ± 1.0 in controls (P < 0.000001). The duration of phase III was 305 ± 123 sec in IBS subjects and 428 ± 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.     

Small Intestinal Bacterial Overgrowth in Patients with Interstitial Cystitis and Gastrointestinal Symptoms

Purpose Interstitial cystitis (IC) often coexists with irritable bowel syndrome (IBS). IBS may be explained by small-intestinal bacterial overgrowth (SIBO), which increases immune activation and visceral hypersensitivity. This prospective pilot study tested hypotheses that IC patients with gastrointestinal (GI) symptoms have SIBO, that nonabsorbable antibiotic use improves symptoms, and that improvement is sustained by prokinetic therapy. Methods Consecutive IC patients with GI symptoms had lactulose breath testing (LBT). Those with abnormal results received rifaximin 1,200–1,800 mg/day for 10 days then tegaserod 3 mg/nightly. Questionnaires addressed IC and GI global improvement. Results Of 21 patients, 17 (81%) had abnormal LBTs. Of 15 patients treated, GI global improvement was moderate to great in 11 (73%) and sustained in ten (67%). IC global improvement was moderate to great in six (40%) and sustained in seven (47%). Conclusions A majority of IC patients and GI symptoms had an abnormal LBT suggesting SIBO. Rifaximin improved symptoms, which was sustained by tegaserod.     

Irritable bowel syndrome and small intestinal bacterial overgrowth:Meaningful association or unnecessary hype

Irritable bowel syndrome(IBS)is a common condition characterized by abdominal pain or discomfort,bloating,and altered stool form and passage.Small intestinal bacterial overgrowth(SIBO)is a condition in which there is overgrowth of bacteria in small bowel in excess of 105colony forming units per milliliter on culture of the upper gut aspirate.Frequency of SIBO varied from 4%-78%among patients with IBS and from 1%-40%among controls.Higher frequency in some studies might be due to fallacious criteria[postlactulose breath-hydrogen rise 20 PPM above basal within 90 min(early-peak)].Glucose hydrogen breath test(GHBT)has a low sensitivity to diagnose SIBO.Hence,studies based on GHBT might have under-estimated frequency of SIBO.Therefore,it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected.This review evaluates studies on association between SIBO and IBS,discordance between different studies,their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.     

A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing

BACKGROUND: An association between irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) has been found. OBJECTIVE: To compare the prevalence and test results for bacterial overgrowth between IBS and fibromyalgia. METHODS: Subjects with independent fibromyalgia and IBS were compared with controls in a double blind study. Participants completed a questionnaire, and a lactulose hydrogen breath test was used to determine the presence of SIBO. The prevalence of an abnormal breath test was compared between study participants. Hydrogen production on the breath test was compared between subjects with IBS and fibromyalgia. The somatic pain visual analogue score of subjects with fibromyalgia was compared with their degree of hydrogen production. RESULTS: 3/15 (20%) controls had an abnormal breath test compared with 93/111 (84%) subjects with IBS (p<0.01) and 42/42 (100%) with fibromyalgia (p<0.0001 v controls, p<0.05 v IBS). Subjects with fibromyalgia had higher hydrogen profiles (p<0.01), peak hydrogen (p<0.0001), and area under the curve (p<0.01) than subjects with IBS. This was not dependent on the higher prevalence of an abnormal breath test. The degree of somatic pain in fibromyalgia correlated significantly with the hydrogen level seen on the breath test (r = 0.42, p<0.01). CONCLUSIONS: An abnormal lactulose breath test is more common in fibromyalgia than IBS. In contrast with IBS, the degree of abnormality on breath test is greater in subjects with fibromyalgia and correlates with somatic pain.