Probiotics in the management of functional bowel disorders: promise fulfilled?

Irritable bowel syndrome (IBS) and chronic constipation (CC) are common problems worldwide and are associated with significant impact on activities of daily living and quality of life. Recent interest, in IBS in particular, has focused on the potential roles of the microbiota and its interaction with the host's immune system. Recently, high-quality clinical trials have been performed on prebiotics and probiotics in IBS or CC. Although strategies that seek to modify the microbiota, such as the use of probiotics, offer much promise in IBS and CC, more high-quality trials and, studies of longer duration are required.

Alterations in the intestinal microbiota and functional bowel symptoms.

Functional gastrointestinal disorders (FGIDs) are highly prevalent in Western countries yet no single mechanism or etiological agent that initiates IBS has been identified. Current research has implicated the intestinal microbiota with FGIDs. This article reviews the available literature/data regarding the intestinal microbiota and FGIDS. The possible relationships between the intestinal microbiota and the intestinal function and functional bowel symptoms are discussed.

[Chronic heart failure: structural and microbiological changes in the colon].

AIM: To study microbiocenosis of the parietal layer of the colon and feces, concentrations of endotoxin and proinflammatory cytokines in patients with chronic heart failure (CHF) of different functional classes vs. healthy subjects of the same age. MATERIAL AND METHODS: The trial includes 37 patients with ischemic CHF and 13 healthy volunteers. The examination comprised 6-min walking test, echocardiographic evaluation of the left ventricular ejection fraction, clinical state by a special scale, assay for C-reactive protein, endotoxin, fecal seeding, colonoscopy with biopsy and seeding. RESULTS: Gram-negative flora in the colon and parietal layer occurred in high concentrations correlating with severity of CHF. The examinees with CHF of functional class III-IV had elevated levels of circulating endotoxin and serum C-reactive protein.

[Post-infectious irritable bowel syndrome. A review based on current evidence]. / Síndrome de intestino irritable postinfeccioso. Una revisión basada en evidencias.

INTRODUCTION: Pathophysiology of irritable bowel syndrome (IBS) is multifactorial. Recent investigations have associated episodes of infectious gastroenteritis with development of IBS. This condition is named post-infectious IBS (PI-IBS). The role of inflammation-infection in IBS pathogenesis is not well understood. AIM: To review published scientific evidence on PI-IBS regarding risk factors, causal agents, histopathological changes, and treatment. MATERIALS AND METHODS: An electronic search in MEDLINE and abstracts presented at national and international GI meetings was performed, looking for information published in the past 50 years including animal studies, cohort studies, case-control studies, and series of cases and case reports, using the key words post-infectious enteritis, post-dysenteric or post-infectious irritable bowel syndrome (PI-IBS), and post-infectious colitis. RESULTS: Fifty one papers were included. These studies were classified according to pathophysiologic mechanisms, infectious agents involved, animal or human studies, and treatment. CONCLUSIONS: Current evidence shows a strong association between colonic infection and inflammation with development of IBS. Approximately 25% of patients with IBS have a history of infectious enteritis. Microbial agents related with PI-IBS include bacteria (Campylobacter, Salmonella) and parasites (Trichinella spiralis). Increased number of enteroendocrine cells, CD3 lymphocytes and mast cells within the colonic muscle wall, release of pro-inflammatory substances, and increased number of inflammatory cells with intestinal nervous endings are the most common histopathologic findings. Patients developing PI-IBS have a higher frequency of psychological disorders and stressful events prior to the gastroenteritis episode. Therapeutic interventions with steroids, COX-2 inhibitors, antibiotics and probiotics require further investigation.

Infection as a cause of irritable bowel syndrome.

The normal response to infection, such as vomiting and diarrhoea, is protective and beneficial. However, in about 10% of patients these protective changes persist and may contribute to the development of post-infective irritable bowel syndrome, which may persist for many years. New insights into the pathogenesis of this condition suggest novel, effective ways of treatment.

Postinfectious irritable bowel syndrome.

A small but significant subgroup of patients with irritable bowel syndrome (IBS) report a sudden onset of their IBS symptoms after a bout of gastroenteritis. Population-based surveys show that although a history of neurotic and psychologic disorders, pain-related diseases, and gastroenteritis are all risk factors for developing IBS, gastroenteritis is the most potent. More toxigenic organisms increase the risk 11-fold, as does an initial illness lasting more than 3 weeks. Hypochondriasis and adverse life events double the risk for postinfective (PI)-IBS and may account for the increased proportion of women who develop this syndrome. PI-IBS is associated with modest increases in mucosal T lymphocytes and serotonin-containing enteroendocrine cells. Animal models and some preliminary human data suggest this leads to excessive serotonin release from the mucosa. Both the histologic changes and symptoms in humans may last for many years with only 40% recovering over a 6-year follow-up. Celiac disease, microscopic colitis, lactose intolerance, early stage Crohn's disease, and bile salt malabsorption should be excluded, as should colon cancer in those over the age of 45 years or in those with a positive family history. Treatment with Loperamide, low-fiber diets, and bile salt- binding therapy may help some patients. Serotonin antagonists are logical treatments but have yet to be evaluated.

[Role of dysbiotic disruption in etiology and pathogenesis of irritable bowel syndrome]. / Rol' disbioticheskikh narushenii v étiologii i patogeneze sindroma razdrazhennogo kishechnika.

Based on the obtained data, it was established that the development of dysbiotic changes in the large and small intestines after enteric infections is a cause for exacerbation of the irritable bowel syndrome.

Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome.

BACKGROUND AND AIMS: Chronic bowel disturbances resembling irritable bowel syndrome (IBS) develop in approximately 25% of patients after an episode of infectious diarrhoea. Although we have previously shown that psychosocial factors operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. To evaluate this further, we measured expressions of interleukin 1beta (IL-1beta) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. METHODS: Sequential rectal biopsy samples were prospectively obtained during and three months after acute gastroenteritis, from eight patients who developed post-infectious IBS (INF-IBS) and seven patients who returned to normal bowel habits after acute gastroenteritis (infection controls, INF-CON). Eighteen healthy volunteers who had not suffered from gastroenteritis in the preceding two years served as normal controls (NOR-CON). IL-1beta and IL-1ra gene expressions were assayed by reverse transcriptase-polymerase chain reaction, and their levels of expression were quantitated by optical densitometry after electrophoresis on agarose gel. RESULTS: INF-IBS patients exhibited significantly greater expression of IL-1beta mRNA in rectal biopsies than INF-CON patients both during and three months after acute gastroenteritis. Moreover, IL-1beta mRNA expression had increased in biopsies taken from INF-IBS patients at three months after the acute infection but no consistent change was observed in INF-CON patients. IL-1beta mRNA expression of INF-IBS patients at three months post gastroenteritis was significantly greater than NOR-CON whereas that of INF-CON patients was not significantly different from NOR-CON. Despite these differential changes in IL-1beta mRNA expression, no significant changes were observed in IL-1ra mRNA expression among the three groups. CONCLUSIONS: These findings indicate that those patients who develop IBS post infection exhibit greater IL-1beta mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS.

A systematic review of alternative therapies in the irritable bowel syndrome.

The irritable bowel syndrome is a common disorder associated with a significant burden of illness, poor quality of life, high rates of absenteeism, and high health care utilization. Management can be difficult and treatment unrewarding; these facts have led physicians and patients toward alternative therapies. We explored a variety of treatments that exist beyond the scope of commonly used therapies for irritable bowel syndrome. Guarded optimism exists for traditional Chinese medicine and psychological therapies, but further well-designed trials are needed. Oral cromolyn sodium may be useful in chronic unexplained diarrhea and appears as effective as and safer than elimination diets. The roles of lactose and fructose intolerance remain poorly understood. Alterations of enteric flora may play a role in irritable bowel syndrome, but supporting evidence for bacterial overgrowth or probiotic therapy is lacking.

Is irritable bowel syndrome more common in patients presenting with bacterial gastroenteritis? A community-based, case-control study.

OBJECTIVE: Irritable bowel syndrome (IBS) has been reported to follow infectious diarrhea. Food-borne infections affect 76 million people in the United States and 9.4 million in England per year; of these, only a small percentage of patients see their doctor, and even fewer will have stool culture confirmation. We hypothesized that patients who present to their doctor with gastroenteritis and have positive stool samples may be different from the normal population with regard to their pre-existing bowel symptoms. Our aim was to determine if patients with bacterial gastroenteritis were more likely to have prior IBS, functional dyspepsia, or functional diarrhea, compared with a control population. METHODS: Between January, 2000 and January, 2001, subjects with stool positive bacterial gastroenteritis and control subjects from the same primary care practice were invited to participate. The main outcome measure was the presence of IBS, functional dyspepsia, or functional diarrhea diagnosed using self-report Rome II modular questionnaires. RESULTS: A total of 217 people with recent bacterial gastroenteritis and 265 community controls consented to participate in the study. Of these, 89/217 cases and 46/265 controls had one of the functional GI disorders (OR = 3.3; 95% CI = 2.17-5.00). IBS was present in 67 cases (31%) and 26 controls (10%) (OR = 4.1; 95% CI = 2.49-6.72). There was no statistically significant difference in the presence of prior functional dyspepsia or functional diarrhea. CONCLUSIONS: IBS is more frequent before diagnosis in people with bacterial gastroenteritis presenting to their primary care physician than in community controls. Studies that examine the rate of IBS after bacterial gastroenteritis need to carefully exclude people with prior IBS in a systematic way.

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.

The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report.

Recent investigations have shown that bacterial overgrowth of the small intestine is associated with a number of functional somatic disorders, including irritable bowel syndrome (IBS), fibromyalgia, and chronic fatigue syndrome. A number of controlled studies have shown that enteric-coated peppermint oil (ECPO) is of benefit in the treatment of IBS. However, despite evidence of strong antimicrobial activity, ECPO has not been specifically investigated for an effect on small intestinal bacterial overgrowth (SIBO). A case report of a patient with SIBO who showed marked subjective improvement in IBS-like symptoms and significant reductions in hydrogen production after treatment with ECPO is presented. While further investigation is necessary, the results in this case suggest one of the mechanisms by which ECPO improves IBS symptoms is antimicrobial activity in the small intestine.

Is lactose intolerance implicated in the development of post-infectious irritable bowel syndrome or functional diarrhoea in previously asymptomatic people?

OBJECTIVE: The relationship between lactose intolerance and post-infectious irritable bowel syndrome (IBS) in adults is uncertain. Bowel symptoms may persist after bacterial gastroenteritis and as post-infectious IBS. Acquired lactose intolerance may follow viral enteric infections in children. We compared the frequency of lactose intolerance after bacterial gastroenteritis in adults with and without symptoms of IBS or functional diarrhoea at 3-6-months' follow-up. DESIGN: A prospective cohort study was conducted. METHODS: All subjects with bacterial gastroenteritis confirmed by stool culture from the microbiology laboratory and without prior IBS or functional diarrhoea were eligible to participate. IBS and functional diarrhoea were diagnosed via self-completed Rome II modular questionnaires. Lactose intolerance was determined from a rise in breath hydrogen and plasma glucose and symptoms. RESULTS: One hundred and twenty-eight subjects with bacterial gastroenteritis were followed prospectively, from which a smaller cohort of 42 subjects took part in this study. The cohort was comprised of 24/25 subjects who developed post-infectious IBS (n = 16) or functional diarrhoea (n = 8) (9 male, 15 female) and 18 random controls (8 male, 10 female) chosen from the group without IBS or functional diarrhoea. The mean age of the subjects was 44.4 years (range 25-76 years). In the group with functional diarrhoea or IBS, four subjects had failure of the plasma glucose to rise but none had abnormal glucose hydrogen breath tests. In the control subjects, one had a positive combined test and six had failure of plasma glucose to rise alone. No subject developed symptoms during the test. CONCLUSIONS: Bacterial gastroenteritis did not cause persistent lactose intolerance in our study population. Lactose intolerance does not appear to be implicated in the aetiology of post-infectious bowel symptoms, including IBS. Advice to avoid dairy products in patients presenting with post-infectious IBS on the basis that they may have lactose intolerance appears unnecessary in patients from northern England.

A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics.

Irritable bowel syndrome (IBS) is a multi-factorial gastrointestinal condition affecting 8-22 % of the population with a higher prevalence in women and accounting for 20-50 % of referrals to gastroenterology clinics. It is characterised by abdominal pain, excessive flatus, variable bowel habit and abdominal bloating for which there is no evidence of detectable organic disease. Suggested aetiologies include gut motility and psychological disorders, psychophysiological phenomena and colonic malfermentation. The faecal microflora in IBS has been shown to be abnormal with higher numbers of facultative organisms and low numbers of lactobacilli and bifidobacteria. Although there is no evidence of food allergy in IBS, food intolerance has been identified and exclusion diets are beneficial to many IBS patients. Food intolerance may be due to abnormal fermentation of food residues in the colon, as a result of disruption of the normal flora. The role of probiotics in IBS has not been clearly defined. Some studies have shown improvements in pain and flatulence in response to probiotic administration, whilst others have shown no symptomatic improvement. It is possible that the future role of probiotics in IBS will lie in prevention, rather than cure.

Evolving concepts in the pathophysiology of functional gastrointestinal disorder.

Functional gastrointestinal disorder (FGID) is common and may affect any part of the digestive tract from the esophagus to the rectum. Functional dyspepsia and the irritable bowel syndrome (IBS) are the most commonly recognized and until recently were considered distinct entities. In recent years, however, new observations and studies of the afferent nervous system have extended our concepts of both IBS and dyspepsia and suggest that these conditions may have common triggers and expression from similar pathophysiological processes.

Irritable bowel syndrome: classification and conceptualization.

The irritable bowel syndrome is one of a group of functional gastrointestinal disorders within the Rome classification system that is characterized by abdominal discomfort or pain associated with a change in stool habit. It is a multidetermined biopsychosocial disorder in which physiological, psychological, behavioral, and environmental factors may contribute to the clinical expression of the disorder. These can include: (1) early life (e.g., genetic or environmental) factors; (2) physiological factors including increased motor reactivity, visceral hypersensitivity, which may be enabled by postinfectious events, and dysregulation of brain-gut communication (e.g., altered central pain control mechanisms). In addition, psychosocial factors including psychiatric co-morbidity, major trauma (e.g., abuse history), and maladaptive coping may amplify the clinical expression of the disorder and its outcome. Currently, clinical outcome has become understood in terms of global symptom relief and health-related quality of life.