Magnus Simren

Intestinal microbiota in functional bowel disorders: a Rome foundation report

It is increasingly perceived that gut host–microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host–microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.

Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors

OBJECTIVES:Quality of life is reduced in inflammatory bowel disease (IBD). Whether or not this is true in IBD patients in long-standing remission is unclear. Symptoms compatible with irritable bowel syndrome (IBS) are common in IBD patients in remission. The importance of psychological factors in this process is a matter of controversy.METHODS:Forty-three patients with ulcerative colitis (UC) and 40 with Crohns disease (CD), who had been in remission for at least 1 yr according to laboratory parameters and clinical and endoscopical appearance, were included. These patients completed four different self-administered questionnaires, evaluating GI symptoms, anxiety, depression, and psychological general well-being. The two patient groups were compared with the general population, and within-group comparisons in psychometric scores were made between patients with and without IBS-like symptoms.RESULTS:The psychological well-being in IBD patients in long-standing remission was similar to that of the general population, despite the presence of more severe GI symptoms. CD patients reported more psychosocial dysfunction, reduced well-being, and GI symptoms than UC patients. Thirty-three percent of UC patients and 57% of CD patients had IBS-like symptoms. The group with IBS-like symptoms (both UC and CD) had higher levels of anxiety and depression and more reduced well-being than those without. Anxiety and reduced vitality were found to be independent predictors for IBS-like symptoms in these patients.CONCLUSION:The prevalence of IBS-like symptoms in IBD patients in long-standing remission is two to three times higher than that in the normal population. Psychological factors seem to be of importance in this process. However, as a group IBD patients in remission demonstrate psychological well-being comparable to that of the general population.

Small intestinal bacterial overgrowth in patients with irritable bowel syndrome

Background: Small intestinal bacterial overgrowth (SIBO) has been proposed to be common in irritable bowel syndrome (IBS), with altered small-bowel motility as a possible predisposing factor. Aim: To assess the prevalence of SIBO, by culture of small-bowel aspirate, and its correlation to symptoms and motility in IBS. Methods: 162 patients with IBS who underwent small-bowel manometry and culture of jejunal aspirate were included. Cultures from 26 healthy subjects served as controls. Two definitions of altered flora were used: the standard definition of SIBO (⩾105 colonic bacteria/ml), and mildly increased counts of small-bowel bacteria (⩾95th centile in controls). Results: SIBO (as per standard definition) was found in 4% of both patients and controls. Signs of enteric dysmotility were seen in 86% of patients with SIBO and in 39% of patients without SIBO (p = 0.02). Patients with SIBO had fewer phase III activities (activity fronts) than patients without SIBO (p = 0.08), but otherwise no differences in motility parameters were seen. Mildly increased bacterial counts (⩾5×103/ml) were more common in patients with IBS than in controls (43% vs 12%; p = 0.002), but this was unrelated to small intestinal motility. No correlation between bacterial alterations and symptom pattern was observed. Conclusions: The data do not support an important role for SIBO according to commonly used clinical definitions, in IBS. However, mildly increased counts of small-bowel bacteria seem to be more common in IBS, and needs further investigation. Motility alterations could not reliably predict altered small-bowel bacterial flora.

An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota

Background and aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that may be triggered by enteric pathogens and has also been linked to alterations in the microbiota and the host immune response. The authors performed a detailed analysis of the faecal microbiota in IBS and control subjects and correlated the findings with key clinical and physiological parameters. Design The authors used pyrosequencing to determine faecal microbiota composition in 37 IBS patients (mean age 37 years; 26 female subjects; 15 diarrhoea-predominant IBS, 10 constipation-predominant IBS and 12 alternating-type IBS) and 20 age- and gender-matched controls. Gastrointestinal and psychological symptom severity and quality of life were evaluated with validated questionnaires and colonic transit time and rectal sensitivity were measured. Results Associations detected between microbiota composition and clinical or physiological phenotypes included microbial signatures associated with colonic transit and levels of clinically significant depression in the disease. Clustering by microbiota composition revealed subgroups of IBS patients, one of which (n=15) showed normal-like microbiota composition compared with healthy controls. The other IBS samples (n=22) were defined by large microbiota-wide changes characterised by an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa. Conclusions Detailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.

Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions.

IBS is one of the most common functional gastrointestinal disorders worldwide and is thought to be the result of disturbed neural function along the brain–gut axis. The mechanisms behind this disturbance are not clear, but important roles for low-grade inflammation and immunological alterations in the development of symptoms compatible with IBS have become evident. The development of long-standing gastrointestinal symptoms after infectious gastroenteritis and patients with IBD in remission frequently having functional gastrointestinal symptoms support this hypothesis. An increased innate immune activity in the intestinal mucosa and in blood is found in subpopulations of patients with IBS. Mast cells and monocytes seem to be particularly important. In addition, studies have demonstrated that IBS may be associated with an activated adaptive immune response. Increased epithelial barrier permeability and an abnormal gut flora might lead to increased activation of the intestinal immune system. Functional and anatomical evidence for abnormal neuroimmune interactions has been found in patients with IBS. The link between immune alterations and severity of gastrointestinal symptoms and the positive effect of anti-inflammatory treatments in IBS further highlight the relevance of neuroimmune interactions in this condition.

Food-Related Gastrointestinal Symptoms in the Irritable Bowel Syndrome

Background/Aims: Postprandial symptoms are common in patients with irritable bowel syndrome (IBS). However, existing studies have come to different conclusions about the role of food in the pathophysiology of IBS. We explored the prevalence of subjective food-related gastrointestinal (GI) symptoms and its relationship to clinical characteristics and psychological factors in IBS. Methods: 330 patients with IBS and 80 healthy volunteers completed a food questionnaire developed for this study. The subjects graded their subjective symptoms after 35 different foods and a food score was obtained by adding the item scores. The relationship between subjective food-related GI symptoms and referral status, IBS subgroup (predominant bowel pattern), sex, anxiety, depression and body mass index (BMI) was estimated. Results: In 209 (63%) of the patients the GI symptoms were related to meals. Gas problems and abdominal pain were the most frequently reported symptoms. Foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices were most frequently reported to cause symptoms. The food score was higher in patients than in controls (p < 0.0001). In the IBS group higher scores were observed in patients with anxiety (p = 0.005), and females (p < 0.001), but the results were unrelated to IBS subgroup, referral status or BMI. The BMI did not differ between groups. Conclusion: A majority of IBS patients consider their symptoms to be related to meals. Especially foods rich in carbohydrates and fat cause problems. Nevertheless, the majority of IBS patients are normal or overweight. Female sex and anxiety predict a high degree of food-related symptoms in IBS.

Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress

Background and aims: Stress often worsens the symptoms of irritable bowel syndrome (IBS). We hypothesised that this might be explained by altered neuroendocrine and visceral sensory responses to stress in IBS patients. Subjects and methods: Eighteen IBS patients and 22 control subjects were assessed using rectal balloon distensions before, during, and after mental stress. Ten controls and nine patients were studied in supplementary sessions. Rectal sensitivity (thresholds and intensity—visual analogue scale (VAS)) and perceived stress and arousal (VAS) were determined. Plasma levels of corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), cortisol, noradrenaline, and adrenaline were analysed at baseline, immediately after stress, and after the last distension. Heart rate was recorded continuously. Results: Thresholds were increased during stress in control subjects (p<0.01) but not in IBS patients. Both groups showed lower thresholds after stress (p<0.05). Repeated distensions without stress did not affect thresholds. Both groups showed increased heart rate (p<0.001) and VAS ratings for stress and arousal (p<0.05) during stress. Patients demonstrated higher ratings for stress but lower for arousal than controls. Basal CRF levels were lower in patients (p<0.05) and increased significantly during stress in patients (p<0.01) but not in controls. Patients also responded with higher levels of ACTH during stress (p<0.05) and had higher basal levels of noradrenaline than controls (p<0.01). Controls, but not patients, showed increased levels of adrenaline and noradrenaline in response to stress (p<0.05). Conclusions: Stress induced exaggeration of the neuroendocrine response and visceral perceptual alterations during and after stress may explain some of the stress related gastrointestinal symptoms in IBS.

Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies

Background  Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy.

An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome

BACKGROUND/AIMS Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS We studied 13 healthy subjects and 16 patients with IBS—eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Self-Reported Food-Related Gastrointestinal Symptoms in IBS Are Common and Associated With More Severe Symptoms and Reduced Quality of Life

OBJECTIVES:Despite the fact that food and diet are central issues, that concern patients with irritable bowel syndrome (IBS), the current understanding about the association between the intake of certain foods/food groups and the gastrointestinal (GI) symptom pattern, psychological symptoms, and quality of life is poor. The aim of this study was to determine which food groups and specific food items IBS patients report causing GI symptoms, and to investigate the association with GI and psychological symptoms and quality of life.METHODS:We included 197 IBS patients (mean age 35 (18–72) years; 142 female subjects) who completed a food questionnaire in which they specified symptoms from 56 different food items or food groups relevant to food intolerance/allergy. The patients also completed questionnaires to assess depression and general anxiety (Hospital Anxiety and Depression), GI-specific anxiety (Visceral Sensitivity Index), IBS symptoms (IBS-Severity Scoring System), somatic symptoms (Patient Health Questionnaire-15), and quality of life (Irritable Bowel Syndrome Quality of Life Questionnaire).RESULTS:In all, 84% of the studied population reported symptoms related to at least one of the food items surveyed. Symptoms related to intake of food items with incompletely absorbed carbohydrates were noted in 138 (70%) patients; the most common were dairy products (49%), beans/lentils (36%), apple (28%), flour (24%), and plum (23%). Of these, 58% experienced GI symptoms from foods rich in biogenic amines, such as wine/beer (31%), salami (22%), and cheese (20%). Histamine-releasing foods, such as milk (43%), wine/beer (31%), and pork (21%), were also considered causes of symptoms in IBS patients. GI symptoms were also frequently reported after intake of fried and fatty foods (52%). With increasing IBS symptom severity, patients reported more food items responsible for their GI symptoms (P=0.004), and this was also found in patients with more severe somatic symptoms (P<0.0001). Women tended to report more food items causing symptoms than men (P=0.06). A high number of food items causing GI symptoms was also associated with reduced quality of life and this was significant for the following domains: sleep (r=−0.25; P=0.001), energy (r=−0.21; P=0.005), food (r=−0.29; P<0.001), social functioning (r=−0.23; P=0.001), and physical status (r=−0.16; P<0.05). However, the number of food items reported to provoke GI symptoms was unrelated to body mass index, age, IBS subtype, anxiety, depression, or GI-specific anxiety.CONCLUSIONS:The majority of IBS patients believe that certain food items are important triggers of their GI symptoms. This is especially true for foods containing carbohydrates and fat, and also may be relevant for histamine-releasing food items and foods rich in biogenic amines. Self-reported food intolerance is associated with high symptom burden and reduced quality of life.