Irritable Bowel Syndrome: Simrén M

Simrén M. · No affiliation provided · Gastroenterology. · Pubmed #19327731 No free full text.

This publication has no abstract.

Gunnarsson J, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #18679389 No free full text.

Abstract: Functional bowel disorders (FBDs) are common disorders that are characterized by various combinations of abdominal pain and/or discomfort, bloating and changes in bowel habits. At present, diagnosing FBDs often incurs considerable health-care costs, partly because unnecessary investigations are performed. Patients are currently diagnosed as having an FBD on the basis of a combination of typical symptoms, normal physical examination and the absence of alarm features indicative of an organic gastrointestinal disease. Basic laboratory investigations, such as a complete blood count, measurement of the erythrocyte sedimentation rate and serological tests for celiac disease, are useful in the initial evaluation. No further investigations are needed for most patients who have typical symptoms and no alarm symptoms. The most important alarm symptoms include signs of gastrointestinal bleeding, symptom onset above 50 years of age, a family history of colorectal cancer, documented weight loss and nocturnal symptoms. The presence of alarm symptoms obviously does not exclude an FBD, but further investigation is needed before confirmation of the diagnosis. For patients with predominant and severe diarrhea, a more thorough diagnostic work-up should normally be considered, including colonoscopy with colonic biopsies and a test for bile-acid malabsorption.

Ohman L, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Dig Liver Dis. · Pubmed #17267314 No free full text.

Abstract: 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.

Posserud I, Ersryd A, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · World J Gastroenterol. · Pubmed #16718806 links to  free full text

Abstract: The pathophysiology of IBS is complex and still incompletely known. Both central and peripheral factors, including psychosocial factors, abnormal GI motility and secretion, and visceral hypersensitivity, are thought to contribute to the symptoms of IBS. Several studies have demonstrated altered GI motor function in IBS patients and the pattern differs between IBS subgroups based on the predominant bowel pattern. Few studies have so far addressed GI secretion in IBS, but there are some evidence supporting altered secretion in the small intestine of IBS patients. Visceral hypersensitivity is currently considered to be perhaps the most important pathophysiological factor in IBS. Importantly, several external and internal factors can modulate visceral sensitivity, as well as GI motility, and enhanced responsiveness within the GI tract to for instance stress and nutrients has been demonstrated in IBS patients. Today IBS 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 alterations probably dominating in some patients and disturbed central processing of signals from the periphery in others.

Simrén M, Stotzer PO. · Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden. · Gut. · Pubmed #16474100 links to  free full text

Abstract: Hydrogen breath tests are widely used to explore the pathophysiology of functional gastrointestinal disorders. Small intestinal bacterial overgrowth and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms in, for instance, irritable bowel syndrome. However, conclusions drawn from these studies are highly controversial and divergent results exist. There is also an extensive use of these tests in clinical practice with difficulties regarding interpretation of the tests and sometimes erroneous conclusions. The limitations and pitfalls of these tests will be reviewed in this article, and hopefully the occasional abuse of these tests can be turned into proper clinical and scientific use instead in the future.

Simrén M. · Dept of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Int J Clin Exp Hypn. · Pubmed #16316884 No free full text.

Abstract: Irritable bowel syndrome (IBS) is a very common condition in the Western part of the world, and it accounts for a large proportion of the workload of a gastroenterologist. Unfortunately, the pathogenesis and pathophysiology of the syndrome are incompletely understood, and the treatment options are limited. However, hypnotherapy is one treatment option that has proven to be very useful in IBS. The mechanisms of action explaining why hypnosis is effective for IBS are not altogether known, but recent studies have shed some light on this issue. These studies, and what can be learned from them about how hypnosis impacts IBS, are reviewed in this article. Hypnosis may affect IBS partly through changes in colorectal sensitivity and improvement in psychological factors. The effects on GI motility and the autonomic nervous system are less clear and need further evaluation.

Simrén M, Brazier J, Coremans G, Dapoigny M, Müller-Lissner SA, Pace F, Smout AJ, Stockbrügger RW, Vatn MH, Whorwell PJ. · Department of Internal Medicine, Sahlgrenska University Hospital, SE-41345 Goteborg, Sweden. · Digestion. · Pubmed #15256832 No free full text.

Abstract: Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.

Ringström G, Störsrud S, Lundqvist S, Westman B, Simrén M. · Dept of Internal Medicine, Institute of medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · BMC Gastroenterol. · Pubmed #19192312 links to  free full text

Abstract: BACKGROUND: Many IBS patients experience that they receive limited information and that the health care system does not take their complaints seriously. We aimed to develop a structured patient education, an 'IBS school', and investigate if the efficacy could be evaluated in terms of improved knowledge, symptom severity and health related quality of life (HRQOL). METHODS: The IBS school consisted of six weekly two hour sessions in a group setting. Five different health care professionals were responsible for one session each. Questionnaires covering patients' experience of the education, perceived knowledge about IBS, gastrointestinal symptoms, and HRQOL, were used for evaluation at baseline and at three, six, and twelve months after education. RESULTS: Twelve IBS patients were included. The patients were overall satisfied with the IBS school. In line with this, the gastrointestinal symptoms, HRQOL, and perceived knowledge about IBS improved significantly after the education. CONCLUSION: An IBS school seems to be a proper method to meet the patients' need of information about IBS and also to improve the patients' gastrointestinal symptoms, HRQOL, and knowledge about IBS. Further controlled studies are now needed in larger numbers of patients to confirm these preliminary results in order to implement this intervention in clinical practice.

Ohman L, Isaksson S, Lundgren A, Simrén M, Sjövall H. · Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. · Clin Gastroenterol Hepatol. · Pubmed #16234043 No free full text.

Abstract: BACKGROUND & AIMS: The mechanisms behind irritable bowel syndrome (IBS) are incompletely understood. Recently several studies have suggested a low-grade colonic inflammation as initiator of the gut dysfunctions recorded in this patient group. The aim of this study was to characterize the phenotype and homing properties of colonic and peripheral blood lymphocytes in patients with IBS. METHODS: Patients with IBS (n=33), defined by the Rome II criteria, were compared with UC patients (n=23) and control subjects (n=15) without gastrointestinal symptoms. Colonic and peripheral blood lymphocytes were analyzed by flow cytometry. Secretion of IFN-gamma from intestinal biopsies was determined by enzyme-linked immunosorbent assay, and immunohistochemical staining of colonic biopsies was performed. RESULTS: IBS patients displayed an increased frequency of peripheral blood CD4+ and CD8+ T cells expressing the gut homing integrin beta7. Accordingly, IBS and UC patients had an augmented frequency of lamina propria CD8+ T cells in the ascending colon as compared with control subjects. The frequency of intestinal T cells expressing integrin beta7+ was unaltered in IBS and UC patients, although the expression of mucosal addressin cell adhesion molecule-1+ endothelium, the ligand for integrin beta7, was increased in the ascending colon of IBS and UC patients as compared with control subjects. CONCLUSIONS: Patients with IBS exhibit an enhanced immune activity in the gut and an increased frequency of integrin beta7+ T lymphocytes in the peripheral blood. Our data further support the hypothesis of IBS being at least partially an inflammatory disorder.

Simrén M, Björnsson ES, Abrahamsson H. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Neurogastroenterol Motil. · Pubmed #15670264 No free full text.

Abstract: Motilin shows cyclic variation with the different phases of the migrating motor complex (MMC). Altered motilin levels have been found in irritable bowel syndrome (IBS) patients, but in these studies motilin levels were analysed without the knowledge of the phases of MMC. We included 13 healthy controls (HC) and 24 patients with IBS [12 diarrhoea-predominant (IBS-D) and 12 constipation-predominant (IBS-C)]. We performed interdigestive and postprandial antroduodenojejunal manometry and blood samples for analysis of motilin were drawn. Group differences in plasma levels of motilin were analysed during mid-phase II, just before the start of phase III (pre-III), during phase I, immediately before the meal and 30 and 60 min after the 500 kcal mixed meal. Higher motilin levels were observed in IBS vs HC in both the interdigestive and postprandial periods (P < 0.05). No significant differences between IBS-C and IBS-D were observed. The cyclic variation of motilin during MMC and the meal response was similar in IBS and controls. IBS patients, irrespective of the predominant bowel habit, demonstrate higher motilin levels than HCs in all phases of the MMC and also after a meal. These findings may bear some pathophysiological importance in IBS and relate to the gastrointestinal dysmotility often seen in these patients.

Simrén M, Ringström G, Björnsson ES, Abrahamsson H. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Psychosom Med. · Pubmed #15039508 links to  free full text

Abstract: OBJECTIVE: Postprandial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response. We investigated whether this response can be affected by hypnotherapy. METHODS: We included 28 patients with irritable bowel syndrome refractory to other treatments. They were randomized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks (N = 14) or were provided with supportive therapy (control group; N = 14). Before randomization and after 3 months, all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion. Colonic sensory thresholds and tonic and phasic motor activity were assessed. RESULTS: Before randomization, reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations. At 3 months, the colonic sensitivity before duodenal lipids did not differ between groups. Controls reduced their thresholds after duodenal lipids for gas (22 +/- 1.7 mm Hg vs. 16 +/- 1.6 mm Hg, p <.01), discomfort (29 +/- 2.9 mm Hg vs. 22 +/- 2.6 mm Hg, p <.01), and pain (33 +/- 2.7 mm Hg vs. 26 +/- 3.3 mm Hg, p <.01), whereas the hypnotherapy group reduced their thresholds after lipids only for pain (35 +/- 4.0 mm Hg vs. 29 +/- 4.7 mm Hg, p <.01). The colonic balloon volumes and tone response at randomization were similar in both groups. At 3 months, baseline balloon volumes were lower in the hypnotherapy group than in controls (83 +/- 14 ml vs. 141 +/- 15 ml, p <.01). In the control group, reduced balloon volumes during lipid infusion were seen (141 +/- 15 ml vs. 111 +/- 19 ml, p <.05), but not after hypnotherapy (83 +/- 14 ml vs. 80 +/- 16 ml, p >.20). CONCLUSION: Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome. These effects may be involved in the clinical efficacy of hypnotherapy in IBS.

Simrén M, Simms L, D'Souza D, Abrahamsson H, Björnsson ES. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteburg, Sweden. · Aliment Pharmacol Ther. · Pubmed #12534414 links to  free full text

Abstract: BACKGROUND: Irritable bowel syndrome patients demonstrate colonic hypersensitivity after duodenal lipid infusion. AIM: To investigate the role of 5-hydroxytryptamine-3 (5-HT3) receptors in this sensory component of the gastrocolonic response in irritable bowel syndrome. METHODS: Fifteen female patients with diarrhoea-predominant irritable bowel syndrome completed a trial with the 5-HT3 receptor antagonist alosetron (1 mg b.d.) or placebo (b.d.) over 15 days, followed by the alternative treatment. Each treatment period was followed by a colonic distension trial before and after duodenal lipids. Changes in colonic thresholds, tone and compliance and viscerosomatic referral pattern after lipids were compared between treatments. RESULTS: With placebo, the colonic thresholds after lipids were significantly reduced for all studied sensations, whereas, with alosetron, the thresholds were significantly reduced only for first sensation and discomfort, but not for gas and pain. The reductions in thresholds did not differ significantly between treatments, but the pain threshold after alosetron tended to be less reduced compared with placebo (P = 0.10). The effects of lipids on tone, compliance and viscerosomatic referral pattern were unaffected by alosetron relative to placebo. CONCLUSIONS: 5-HT3 receptor antagonism reduces the lipid-induced colonic hypersensitivity in irritable bowel syndrome. However, 5-HT3 receptors do not seem to be the principal mediator, but may be a cofactor for the exaggerated sensory component of the gastrocolonic response in irritable bowel syndrome.

Simrén M, Abrahamsson H, Björnsson ES. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Gut. · Pubmed #11115818 links to  free full text

Abstract: 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.

Posserud I, Svedlund J, Wallin J, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · J Psychosom Res. · Pubmed #19379956 No free full text.

Abstract: OBJECTIVE: Irritable bowel syndrome (IBS) patients are suggested to selectively attend to gastrointestinal (GI) sensations compared with healthy controls. However, it remains unclear whether there are differences between IBS and other chronic GI disorders. We aimed to evaluate the presence of hypervigilance towards the GI tract in IBS compared with patients with organic GI diseases. METHODS: We included 36 IBS patients and 40 age- and gender-matched patients with organic GI disease. They completed the Hospital Anxiety and Depression Scale (HADS) and underwent three tests: (1) word association-write down as many words as possible representing signs of disease; (2) word recognition (tachistoscope)-four categories of words (positive affects, non-GI symptoms, GI symptoms, negative affects) displayed for increasing time until identified; (3) word recollection-memorize words (10 GI symptoms, 10 positive affects, 10 negative affects). RESULTS: The word-association task did not show group differences. IBS patients were significantly faster than organic GI patients at recognizing words representing GI symptoms (21 vs. 26 ms; P=.04) and negative affects (27 vs. 34 ms; P=.03), but also tended to be faster at recognizing positive affects (24 vs. 29 ms; P=.08) and non-GI symptoms (22 vs. 27 ms; P=.2). Both groups remembered a similar number of words, but IBS patients tended to recall more incorrect GI words than organic patients (1.3 vs. 1.0; P=.06). There were no group differences in HADS scores. CONCLUSION: Compared to patients with organic GI disease, IBS patients seem to be hypervigilant for information regarding GI sensations and maybe also negative information.

Ohman L, Isaksson S, Lindmark AC, Posserud I, Stotzer PO, Strid H, Sjövall H, Simrén M. · Department of Internal Medicine, Institute of Medicine, The Sahlgren's Academy, University of Gothenburg, Gothenburg, Sweden. · Am J Gastroenterol. · Pubmed #19367268 No free full text.

Abstract: OBJECTIVES: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients. METHODS: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed. RESULTS: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity. CONCLUSIONS: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.

Abrahamsson H, Ostlund-Lindqvist AM, Nilsson R, Simrén M, Gillberg PG. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Scand J Gastroenterol. · Pubmed #18788050 No free full text.

Abstract: OBJECTIVE: Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. MATERIAL AND METHODS: Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference < or =4.3 days) and stool frequency were measured. C4 (7-alpha-hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. RESULTS: When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p <0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p <0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. CONCLUSIONS: Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.

Forshammar J, Isaksson S, Strid H, Stotzer PO, Sjövall H, Simrén M, Ohman L. · Department of Medicine, Sahlgrenska Academy of Göteborg University, Sweden. · Scand J Gastroenterol. · Pubmed #18663666 No free full text.

Abstract: OBJECTIVE: Low-grade gastrointestinal inflammation has been reported in patients with irritable bowel syndrome (IBS). However, the colonic B-cell pattern has not been investigated in these patients. Therefore, the aim of this pilot study was to investigate the distribution and isotype of immunoglobulin-producing B cells in the colonic mucosa of IBS patients. MATERIAL AND METHODS: Patients with IBS (n=12) fulfilling the Rome II criteria were compared with controls (n=11). Immunohistochemical staining of biopsies from the sigmoid and ascending colon was performed. RESULTS: The number of IgA(+) B cells in the ascending colon was lower in IBS patients than in controls (p=0.039). Furthermore, unlike controls, IBS patients had a reduction of IgA(+) B cells in the ascending colon relative to the sigmoid colon (p=0.04). Neither the IgG(+), nor the IgM(+) colonic B-cell numbers differed between IBS patients and controls. Very few colonic IgE(+) cells were detected and there was no difference between the two subject groups. CONCLUSIONS: The reduced number of colonic IgA(+) B cells in IBS patients suggests that the disorder may be associated with a modified gut immune defence. Whether this phenomenon is causally related to symptoms remains unknown and merits further investigation in a larger group of patients.

Niklasson A, Strid H, Simrén M, Engström CP, Björnsson E. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Eur J Gastroenterol Hepatol. · Pubmed #18334878 No free full text.

Abstract: BACKGROUND: Symptoms of gastro-oesophageal reflux disease (GERD) have previously been shown to be of importance in patients with asthma. Limited data, however, exist on the prevalence of GERD in patients with chronic obstructive pulmonary disease (COPD), and information about the occurrence of the total burden of gastrointestinal (GI) symptoms in these patients is lacking. METHODS: A total of 113 patients with COPD completed four self-administered questionnaires: the Gastrointestinal Symptom-Rating Scale (GSRS), ROME II modular questionnaires (criteria for irritable bowel syndrome), the Psychological General Well-Being index (PGWB), and the Hospital Anxiety and Depression scale. Eighty-two patients with chronic renal failure (CRF) and 2000 healthy individuals from the general Swedish population served as controls. RESULTS: The total GSRS score in patients with COPD was 2.12 (1.92-2.28) which was significantly higher than the score from the general population of 1.96 (1.81-2.12). No significant difference between COPD and CRF patients was, however, observed, in any of the GSRS dimensions. Patients in the COPD group had lower total PGWB scores compared both with CRF patients 90 (78-104) vs. 98 (83-113) (P<0.05) and with the general population 103 (102-104) (P<0.001). A negative correlation between the GSRS and PGWB scores (r=-0.49; P<0.001) was observed in patients with COPD. Sixteen (14%) of the patients with COPD fulfilled the Rome II criteria for irritable bowel syndrome. CONCLUSION: The prevalence of GI symptoms is higher in patients with COPD than in healthy individuals, but not higher than in CRF patients. The GI symptoms are associated with impairments in psychological well-being, and they require diagnostic workups to explore different treatment options in these patients.

Posserud I, Syrous A, Lindström L, Tack J, Abrahamsson H, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Gastroenterology. · Pubmed #17919487 No free full text.

Abstract: BACKGROUND & AIMS: Diverging results exist regarding the connection between altered visceral perception and gastrointestinal (GI) symptoms, as well as the effects of psychological status on visceral sensitivity. We sought to investigate different aspects of rectal perception in irritable bowel syndrome (IBS) and the association with GI and psychological symptoms. METHODS: We included 109 patients with IBS meeting Rome II criteria (77 women; age range, 20-71 years) and 29 healthy controls (21 women; age range, 20-68 years). They underwent rectal balloon distentions determining sensory thresholds for discomfort and pain, the perceived intensity of unpleasantness, and the viscerosomatic referral area. The fifth percentile (thresholds) and 95th percentile (unpleasantness and referral area) in controls were used to define altered perception. Questionnaires were used to assess severity of IBS-related GI symptoms and psychological symptoms. RESULTS: When combining the 3 aspects of perception, 67 patients (61%) had altered rectal perception. These patients, compared with normosensitive patients, more frequently reported moderate or severe pain (73% vs 44%; P < .01), bloating (73% vs 36%; P < .0001), diarrhea (47% vs 21%; P < .01), satiety (39% vs 13%; P < .01), and clinically significant anxiety (31% vs 12%; P < .05). In a multivariate analysis, only pain and bloating remained associated with altered rectal perception. CONCLUSIONS: Altered rectal perception is common in IBS and seems to be one important pathophysiologic factor associated with GI symptom severity in general and pain and bloating in particular. It is not just a reflection of the psychological state of the patient.

Larsson MH, Simrén M, Thomas EA, Bornstein JC, Lindström E, Sjövall H. · Department of Integrative Pharmacology, Gastrointestinal Biology, AstraZeneca R&D, Mölndal, Sweden. · Neurogastroenterol Motil. · Pubmed #17883433 No free full text.

Abstract: The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role of submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), and its linkage with fasting motor activity [migrating motor complex (MMC)] in controls (n = 16) and patients with IBS [n = 23, 14 diarrhoea predominant (d-IBS) and nine constipation predominant (c-IBS)]. Transmural-PD and its relation to MMC phase III was measured by modified multilumen manometry for 3 h in the fasting state using one jejunal and one duodenal infusion line as flowing electrodes. The amplitude and duration of motor phase III was similar in controls and IBS patients, but the propagation speed of phase III was higher in IBS patients. In IBS patients, maximal PD during MMC phase III was significantly elevated in both the duodenum and jejunum (P < 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P < 0.01). The PD elevation was seen in both duodenum and jejunum in d-IBS patients, but only in the jejunum in the c-IBS patients. On the basis of previous modelling studies, we propose that the enhanced secretion may reflect disturbed enteric network behaviour in some patients with IBS.

Ringström G, Abrahamsson H, Strid H, Simrén M. · Department of Internal Medicine, Section of Gastroenterology & Hepatology, Sahlgrenska University Hospital, Göteborg, Sweden. · Scand J Gastroenterol. · Pubmed #17852851 No free full text.

Abstract: OBJECTIVE: Irritable bowel syndrome (IBS) is common in the population, but not all subjects seek professional health care for their symptoms. The aim of this study was to compare consulters in secondary/tertiary care with those in primary care and non-consulters by using questionnaires to investigate factors of importance for health-care seeking in IBS. MATERIAL AND METHODS: The study included 218 subjects with IBS: 70 non-consulters, 53 patients from primary care and 95 from secondary/tertiary care. The subjects completed questionnaires on gastrointestinal (GI) and psychological symptoms, coping resources, health-related quality of life (HRQOL) and reasons for not seeking health care. RESULTS: Consulters (primary and secondary/tertiary care combined) had poorer HRQOL, more severe psychological symptoms, higher levels of GI-specific anxiety and poor coping resources compared with non-consulters, but the GI symptom severity was similar. Mental health and poor social, emotional and physical functioning were independently predictive of being a health-care seeker (r (2)=0.41). Independent predictors for being a consulter in secondary/tertiary care were a high degree of anxiety, low scores on physical functioning, physical role and food (IBSQOL) (r (2)=0.65). Several non-consulters reported mild symptoms and ability to control symptoms as reasons for not seeking health care. Having a close relative with similar symptoms reduced the need to seek health care. Thirty-six non-consulters had sought alternative care or advice from friends and/or relatives about their GI symptoms. CONCLUSIONS: GI symptom severity alone cannot explain the illness behavior in IBS. HRQOL and psychological symptoms are important for experience of GI symptoms and the health-care seeking pattern in IBS.

Ersryd A, Posserud I, Abrahamsson H, Simrén M. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Aliment Pharmacol Ther. · Pubmed #17767480 No free full text.

Abstract: BACKGROUND: The agreement between subtyping irritable bowel syndrome (IBS) patients based on Rome II criteria versus Rome III criteria is unknown. AIM: To compare IBS subtyping based on Rome II versus III criteria. METHODS: The Rome II Modular Questionnaire and the Bristol Stool Form Scale (one-week diary cards) were completed by 249 IBS patients. Based on the Rome II criteria, patients were defined as having diarrhoea- or constipation-predominant IBS, or alternating IBS. Based on the Rome III criteria, patients were divided into IBS with constipation, IBS with diarrhoea, mixed IBS or unsubtyped IBS. Agreement between Rome II and Rome III was assessed with kappa statistics. RESULTS: Based on Rome II there were 92 diarrhoea-predominant IBS, 45 constipation-predominant IBS and 112 alternating IBS, and based on Rome III 97 IBS with diarrhoea, 77 IBS with constipation, 16 mixed IBS and 59 unsubtyped IBS. The agreement between Rome II and Rome III subgroups was 46% (kappa = 0.19). Changes from the constipation to the diarrhoea subgroups and vice versa were uncommon (8% of patients). The majority of changes occurred from/to the alternating IBS, mixed IBS and unsubtyped IBS subgroups. CONCLUSION: There is poor agreement between subtyping of IBS patients based on Rome II versus Rome III criteria.

Holmén N, Isaksson S, Simrén M, Sjövall H, Ohman L. · Department of Internal Medicine, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. · Neurogastroenterol Motil. · Pubmed #17244166 No free full text.

Abstract: The aetiology of the irritable bowel syndrome (IBS) is incompletely understood. A low-grade colonic inflammation is frequently seen, but it is unclear to what extent this phenomenon contributes to the pathophysiology of IBS. CD4(+)CD25(+) regulatory T cells (Treg) are implicated to play an important role in suppressing intestinal inflammation. We, therefore, examined whether the intestinal inflammatory process in IBS patients is the result of an altered function and/or frequency of CD25(+) Treg cells. Patients with IBS (n = 34), fulfilling the Rome II criteria, were compared with controls (n = 26). The suppressive activity of blood CD25(+) Treg cells was determined and the frequency of colonic and blood CD25(+) Treg cells was analysed by flow cytometry. The expression of the Treg marker, FOXP3 mRNA, in colonic biopsies was determined by reverse transcription-polymerase chain reaction. Blood CD25(+) Treg cells from IBS patients suppressed the proliferation of blood CD4(+)CD25(low/-) T cells. Similar frequencies of CD25(+) Treg cells were recorded in mucosa and blood of IBS patients and controls. FOXP3 mRNA was equally expressed in the colonic mucosa of patients with IBS and controls. In conclusion, the low-grade intestinal inflammation recorded in patients with IBS is not associated with an altered function or frequency of CD25(+) Treg cells.

Simrén M, Agerforz P, Björnsson ES, Abrahamsson H. · Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Göteborg, Sweden. · Neurogastroenterol Motil. · Pubmed #17187585 No free full text.

Abstract: Food-related gastrointestinal symptoms are common in irritable bowel syndrome (IBS), but the mechanisms behind this are unclear. Enhanced colorectal sensitivity after duodenal lipid administration in IBS patients has been demonstrated. However, the effects of a regular meal on colorectal sensitivity in these patients and the importance of the composition of the meal are not known. On two separate days, 10 IBS patients and 11 controls randomly received a liquid meal (800 kcal), containing 60% calories from fat (fatty meal) or carbohydrate (carbohydrate meal). Using a barostat rectal sensitivity was assessed during four separate distension sequences before, immediately after and 30 and 60 min after the meal. In the patients, the discomfort (P = 0.04) and the pain thresholds (P = 0.007) were gradually reduced after the fatty meal, whereas only a tendency in the same direction was seen after the carbohydrate meal. In patients VAS ratings for pain increased after the fatty meal (P = 0.03), but not after carbohydrates. In the controls, sensory thresholds were not affected by the meals. In IBS, a liquid meal enhances rectal sensitivity, and this seems to be partly nutrient dependent as a fatty meal has more pronounced effects than a carbohydrate meal. This might be of relevance for their postprandial symptoms.

Simrén M, Abrahamsson H, Björnsson ES. · Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Clin Gastroenterol Hepatol. · Pubmed #17174611 No free full text.

Abstract: BACKGROUND & AIMS: Duodenal lipid infusion increases colonic hypersensitivity in irritable bowel syndrome (IBS). Whether this is affected by bowel habit, psychologic factors, or sex is unknown. METHODS: We included 61 patients with IBS (50 women, 11 men), 25 with diarrhea-predominant IBS, 17 with constipation-predominant IBS, 19 with alternating-type IBS, and 20 healthy controls (15 women, 5 men). A colonic distension trial was performed with a barostat before and after a 1-hour duodenal lipid infusion (3 kcal/min). Colonic thresholds, colonic tone, and the viscerosomatic referral pattern were assessed and compared between groups. Patients also completed the Hospital Anxiety and Depression scale. RESULTS: The reduction in colonic pressure thresholds after vs before duodenal lipids was greater in patients than in controls for discomfort (P = .006) and pain (P < .0001). An increased viscerosomatic referral area for pain and discomfort during colonic distensions after vs before duodenal lipids was observed in patients but not in controls. The response was similar in IBS subgroups based on the predominant bowel habit, in patients with vs without anxiety and/or depression, and in women and men with IBS. The colonic tone response during lipid infusion was similar in IBS patients and controls, and in the different IBS subgroups. CONCLUSIONS: IBS patients show increased colonic sensitivity and altered viscerosomatic referral pattern after duodenal lipids. This response is largely unaffected by the predominant bowel habit, psychologic factors, or sex, but seems to be related to IBS per se.