Search

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+CD25low/− 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. [ABSTRACT FROM AUTHOR]

Physical activity has become popular in our sedentary society. Gastrointestinal (GI) symptoms are common during exercise among well-trained athletes and joggers. Objective: The aim of the present review is to summarise the current knowledge of the mechanisms behind the changes of gastrointestinal function during exercise. Data sources: The electronic databases of PubMed and SPORTDiscus were searched for original research articles and literature reviews using the terms exercise, physical activity, gastrointestinal function and gastrointestinal tract. Searches of the library catalogue for older articles and reviews were also performed. Study selection: Journal articles, abstracts and books containing relevant information about exercise and gastrointestinal function were reviewed and selected. Data extraction: From these investigations and other data sources the analysed variables and the main outcomes were examined. Data synthesis and conclusion: The effects of physical activity on the gastrointestinal tract were categorised by logical groupings of similar mechanisms. In the reviewed articles there is general consensus that exercise has probably both beneficial and harmful effects on the GI tract, depending partly on the training effect. The reasons behind these somewhat discrepant effects are not understood fully. Altered splanchnic blood flow, effects on GI motor function, neuroendocrine changes, and mechanical effects are mainly involved. There is probably a considerable linkage between these suggested mechanisms; however, more studies are needed to understand the relationship between exercise intensity and duration, and positive and negative alterations in GI physiology. [ABSTRACT FROM AUTHOR]

Summary 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-HT 3 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. [ABSTRACT FROM AUTHOR]

The propagation pattern of individual pressure waves in the gastroduodenal area in IBS is unexplored. We performed antroduodenojejunal manometry on 26 patients with IBS--13 with diarrhea predominant IBS (IBS-D) and 13 with constipation predominant IBS (IBS-C)--and 32 healthy controls. Neuropathic-like motor abnormalities were found in 38% of the patients with conventional manometric evaluation. With high-resolution analysis additional abnormalities were observed in the majority of the patients, with increased frequency of retrograde pressure waves postprandially in both IBS subgroups and in phase II in IBS-D. A correlation between subjective gastrointestinal symptoms and the frequency of retrograde pressure waves in phase II in IBS-D was demonstrated. Motility indices and the number of long clusters were also higher in patients compared to controls. To conclude, an abnormal propagation pattern of individual duodenal pressure waves in IBS patients was demonstrated and found to be related to symptom severity in diarrhea-predominant IBS. High-resolution analysis adds information to standard manometry. [ABSTRACT FROM AUTHOR]

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and this interaction is mediated via the recognition of the conserved Rv2623 pT237-containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant PIM profiles and the opposing in vivo growth phenotypes of ΔRv2623 and ΔRv1747, together with the annotated lipooligosaccharide exporter function of Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial growth by negatively regulating the activity of Rv1747; and that Rv1747 might function as a transporter of PIMs. Because these glycolipids are major mycobacterial cell envelope components that can impact on the immune response, our findings raise the possibility that Rv2623 may regulate bacterial growth, virulence, and entry into persistence, at least in part, by modulating the levels of bacillary PIM expression, perhaps through negatively regulating the Rv1747-dependent export of the immunomodulatory PIMs to alter host-pathogen interaction, thereby influencing the fate of M. tuberculosis in vivo.

An editorial is presented in which the authors provide insights with regard to their sub-grouping approach in the case of irritable bowel syndrome (IBS). Topics discussed include the documentation of the complexity and heterogeneity of IBS, the economic impact and treatment options for the syndrome. Topics including the less understanding of the syndrome's pathophysiology and the things to consider with regard to the testing of their approach, are discussed.

Abstract Background Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI) tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (OXT) and its receptor (OXTR) genes in patients with GI complaints without visible organic abnormalities. Methods Genetic variants in the OXT promoter region, and in the OXTR gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS), 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235) genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the OXT gene (rs6133010 A>G) and 4 related to the OXTR gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T) were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays. Results There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G OXT promoter A/G genotype tended to be more common in the 154 non-persistent (27.3%) subjects than in the 254 lactase persistant (18.1%) subjects and in the healthy controls (19.4%) (p = 0.08). When direct comparing, the A/G genotype was less common in the OXT promoter region in controls (p = 0.09) and in subjects with lactase persistence (p = 0.03) compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the OXT promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%). No significant differences in frequencies of the investigated OXTR SNPs were noted in this study. Conclusion The results suggest that polymorphism in the promoter region of the OXT gene is most common in subjects with lactase non-persistence. This polymorphism may not be related to GI symptoms, as it is related to lactase non-persistence also in healthy controls.

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.

Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19+ B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A response by M. Simren and colleagues to a letter to the editor about their article on the potential role of small intestinal bacterial overgrowth in irritable bowel syndrome is presented.

Treatments for functional constipation ( FC) and irritable bowel syndrome with constipation ( IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum. [ABSTRACT FROM AUTHOR]

Background The etiology of recurrent abdominal pain of functional origin ( AP) is largely unknown. Antibiotic treatment influences the intestinal microbiota, and a few studies have indicated an increased risk of AP in adults after antibiotic treatment. Corresponding data in children are lacking. The aim of this study was to explore the association between antibiotic treatment during childhood and AP at 12 years. Methods Two thousand seven hundred and thirty-two children from a Swedish, population-based birth cohort. Parents reported antibiotic use for the children between birth and 2 years. Antibiotic use between 9 and 12 years was collected from the Swedish Prescribed Drug Register. The children answered questionnaires regarding AP at age 12. We used logistic regression to calculate odds ratios ( ORs) and 95% confidence intervals ( CIs) for AP at 12 years as a function of antibiotic use. Key Results Antibiotic treatment between 9 and 12 years was not associated with AP at 12. Children who had received ≥3 courses, or broad-spectrum antibiotics between 9 and 12 years had an increased risk of AP at 12, but these associations failed to reach statistical significance. Antibiotic treatment during both the first and the second year of life increased the risk of AP in girls at 12 ( OR 1.65; 95% CI: 1.09-2.49), but not in boys or the whole cohort. Conclusions & Inferences Antibiotic treatment does not seem to be a major risk factor for AP at 12 years. However, we cannot exclude that repeated courses, especially to infant girls, or use of broad-spectrum antibiotics between 9 and 12 years may be associated with an increased risk of AP. [ABSTRACT FROM AUTHOR]

Abstract: Background: End‐of‐day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient‐reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross‐cultural adaptation. Methods: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward‐and‐back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients’ understanding with the final items. Key results: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. Conclusions and Inferences: An ESM‐based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross‐cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow. [ABSTRACT FROM AUTHOR]

Background As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. Aim To establish the definition of failure of a treatment to provide adequate relief (F- PAR) to support this management and referral process in patients with chronic constipation. Methods We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. Results The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). Conclusions We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief. [ABSTRACT FROM AUTHOR]

Background Visceral hypersensitivity and psychological symptoms are frequent features in irritable bowel syndrome ( IBS). Exploring mechanistic pathways leading to visceral hypersensitivity is of importance to direct future studies and treatment options. In this study, we evaluated the contribution of psychological factors to the perception of painful and non-painful rectal sensations in hyper- vs normosensitive IBS patients. Methods We included 138 IBS patients (Rome II criteria) who underwent an ascending method of limited rectal balloon distension paradigm. At the end of each distension step, subjects rated the perceived intensity of non-painful ('unpleasantness') and painful rectal sensations on visual analog scales. Sensitivity status was determined based on pain thresholds. Anxiety, depression and somatization were assessed by questionnaires. Mixed models were used to test the relationship between sensitivity status, psychological variables, and pain & unpleasantness ratings upon increasing distension. Key Results Hypersensitive IBS patients had lower sensory thresholds for pain, first perception, urge to defecate, and discomfort ( p < 0.0001). Upon increasing distension, they rated both painful and non-painful sensations as more intense than normosensitive patients ( p < 0.0001). Psychological factors were associated with higher pain ratings during distension in hypersensitive ( p < 0.006-0.0001), but not in normosensitive patients. Anxiety, but not depression or somatization, was associated with increased intensity ratings of non-painful sensations ( p < 0.001), independent of sensitivity status. Conclusions & Inferences Hypersensitive IBS patients are characterized by increased perception of pain, but also of non-painful sensations. Psychological factors increase the perception of painful sensations in hypersensitive patients only, whereas non-painful visceral sensations were exaggerated in anxious patients regardless of the sensitivity status. [ABSTRACT FROM AUTHOR]

Background Dysbiosis is associated with many diseases, including irritable bowel syndrome ( IBS), inflammatory bowel diseases ( IBD), obesity and diabetes. Potential clinical impact of imbalance in the intestinal microbiota suggests need for new standardised diagnostic methods to facilitate microbiome profiling. Aim To develop and validate a novel diagnostic test using faecal samples to profile the intestinal microbiota and identify and characterise dysbiosis. Methods Fifty-four DNA probes targeting ≥300 bacteria on different taxonomic levels were selected based on ability to distinguish between healthy controls and IBS patients in faecal samples. Overall, 165 healthy controls (normobiotic reference collection) were used to develop a dysbiosis model with a bacterial profile and Dysbiosis Index score output. The model algorithmically assesses faecal bacterial abundance and profile, and potential clinically relevant deviation in the microbiome from normobiosis. This model was tested in different samples from healthy volunteers and IBS and IBD patients ( n = 330) to determine the ability to detect dysbiosis. Results Validation confirms dysbiosis was detected in 73% of IBS patients, 70% of treatment-naïve IBD patients and 80% of IBD patients in remission, vs. 16% of healthy individuals. Comparison of deep sequencing and the GA-map Dysbiosis Test, (Genetic Analysis AS, Oslo, Norway) illustrated good agreement in bacterial capture; the latter showing higher resolution by targeting pre-determined highly relevant bacteria. Conclusions The GA-map Dysbiosis Test identifies and characterises dysbiosis in IBS and IBD patients, and provides insight into a patient's intestinal microbiota. Evaluating microbiota as a diagnostic strategy may allow monitoring of prescribed treatment regimens and improvement in new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background Differences regarding symptoms, coping abilities, and quality of life ( QOL) between men and women with irritable bowel syndrome ( IBS) have been reported but data are sparse and sometimes conflicting. The aim of present study was to investigate gender differences in gastrointestinal, extra-intestinal, and psychological symptoms, and sense of coherence ( SOC) and QOL in a large group of patients diagnosed with IBS. Methods We analyzed questionnaire data from 557 patients (152 men) diagnosed with IBS consecutively included in studies at an outpatient clinic for functional bowel disorders between 2002 and 2010. Following questionnaires were included: IBS severity scoring system ( IBS- SSS), Hospital Anxiety and Depression Scale ( HAD), IBSQOL Scale, Visceral Sensitivity Index ( VSI), SOC Scale, Bristol Stool Form Scale ( BSFS), and Patient Health Questionnaire ( PHQ-15). Key Results Women had harder stools ( FDR-adjusted p-value: q = 0.033), more severe bloating ( q = 0.020), higher symptom severity ( q = 0.042), higher total somatic symptom burden ( q = 0.035), lower SOC ( q = 0.042), and lower QOL. Women rated more general anxiety ( q = 0.017) and gastrointestinal-specific anxiety ( q = 0.042), but there were no group differences in depression, pain, stool frequency, impact on daily life, dissatisfaction with bowel habit, or extra-colonic symptoms. The differences found were small (effect sizes: r < 0.3). Conclusions & Inferences In this study, we demonstrated more similarities than differences between men and women with IBS. The largest difference were seen for QOL which might reflect certain structural stressors to which women in general are more exposed than men. [ABSTRACT FROM AUTHOR]

Background Allergy and immune dysregulation may have a role in the pathophysiology of recurrent abdominal pain of functional origin, but previous studies of allergy-related diseases and abdominal pain have contradictory results. Aim To examine the association between allergy-related diseases or sensitisation during childhood and abdominal pain at age 12 years. Methods In this birth cohort study of 4089 children, parents answered questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity ('allergy-related diseases') at ages 0,1,2,4,8 and 12 years. Blood for analyses of allergen-specific IgE was sampled at 4 and 8 years. At 12 years, the children answered questions regarding abdominal pain. Children with coeliac disease or inflammatory bowel disease were excluded. Associations were examined using multivariable logistic regression. Results Among 2610 children with complete follow-up, 9% ( n = 237) reported abdominal pain at 12 years. All allergy-related diseases were associated with concurrent abdominal pain at 12 years and the risk increased with increasing number of allergy-related diseases ( P for trend <0.001). Asthma at 1 and 2 years and food hypersensitivity at 8 years were significantly associated with abdominal pain at 12 years. There was an increased risk of abdominal pain at 12 years in children sensitised to food allergens at 4 or 8 years, but in stratified analyses, this was confined to children whose parents had not reported food hypersensitivity at time of sensitisation. Conclusion Allergy-related diseases as well as sensitisation to food allergens were associated with an elevated risk of abdominal pain, and the risk increased with the number of allergy-related diseases. [ABSTRACT FROM AUTHOR]

Background Irritable bowel syndrome ( IBS) is a functional gastrointestinal disorder of unknown etiology; although infection and inflammation have recently been considered as important etiologic agents. A recent meta-analysis showed correlations between cytokine [interleukin-10 ( IL-10) and tumor necrosis factor ( TNF)] gene polymorphisms and IBS; however, it is still unknown whether patients with IBS have different cytokine profiles compared to healthy population. Methods To determine the relationships between serum/plasma levels or mucosal expression of IL-10/ TNF- α and IBS, we conducted a systematic review and meta-analysis based on case-control studies retrieved from PubMed and EMBASE search through August 2013. Standardized mean difference ( SMD) was generated by using the inverse variance method. Heterogeneity was assessed based on I2 values. Key Results Serum/plasma levels of TNF- α tended to be higher in IBS vs controls ( p = 0.09); this reached significance in IBS subtypes vs controls and in female patients with IBS. However, serum/plasma levels of IL-10 were not significantly different in IBS patients vs controls. Further analysis of serum/plasma IL-10 levels in IBS subtypes did not show any difference; however, analysis based on gender showed a significantly lower serum/plasma IL-10 levels in male patients with IBS vs male controls ( p = 0.02). Colonic IL-10 m RNA had a significantly lower expression in IBS vs control ( p = 0.001). Conclusions & Inferences There is an imbalance of proinflammatory TNF- α, and anti-inflammatory IL-10, cytokines in IBS. Stratifying IBS patients based on cytokine profile may represent an opportunity for personalized treatment of this condition. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: It has been shown that patients with type 1 diabetes mellitus and gastrointestinal (GI) symptoms have abnormal processing of sensory information following stimulation in the oesophagus. In order to find less invasive stimuli to study visceral afferent processing and to further elaborate the gut–brain network in diabetes, we studied brain networks following rectal electrical stimulations. Methods: Twelve type 1 diabetes patients with GI symptoms and twelve healthy controls were included. A standard ambulatory 24-h electrocardiography was performed. 122-channel-evoked brain potentials to electrical stimulation in the rectum were recorded. Brain source-connectivity analysis was done. GI symptoms were assessed with the gastroparesis cardinal symptom index and quality of life (QOL) with SF-36. Any changes in brain source connectivity were correlated to duration of the disease, heart beat-to-beat intervals (RRs), clinical symptoms, and QOL of the patients. Results: Diabetic patients with GI symptoms showed changes relative to controls in the operculum–cingulate network with the operculum source localized deeper and more anterior (P ⩽0.001) and the cingulate source localized more anterior (P =0.03). The shift of operculum source was correlated with the duration of the disease, severity of GI symptoms, and decreased RR (P <0.05). The shift of the cingulate source was correlated with the mental QOL (P =0.04). In healthy controls, the contribution of the cingulate source to the network was higher than the contribution of the operculum source (P ⩽0.001), whereas in patients the contribution of the two sources was comparable. Conclusion: This study gives further evidence for CNS involvement in diabetes. Since network reorganizations were correlated to GI symptoms, irregularities of rectal-evoked potentials can be viewed as a proxy for abnormal bottom-up visceral afferent processing. The network changes might serve as a biomarker for disturbed sensory visceral processing of GI symptoms in diabetes patients. [Copyright &y& Elsevier]

Background Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. Methods We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week−1, 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. Key Results After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group. Conclusions & Inferences Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option. [ABSTRACT FROM AUTHOR]

Background: Abdominal pain can be an overlooked symptom in patients with ulcerative colitis (UC)., Aims: The aim of this study was to investigate the prevalence and factors associated with abdominal pain in active and quiescent UC., Methods: Three study cohorts of adult UC patients were used. Cross-sectional cohorts I and II included 130 (46 active) and 288 (156 active) patients. Longitudinal cohort III included 83 patients with active disease at diagnosis that reached deep remission during follow-up. The Gastrointestinal Symptom Rating Scale was used to assess abdominal pain and other validated questionnaires to assess psychological distress, fatigue and quality of life (QoL)., Results: In the two cross-sectional cohorts, 63% and 58% of the active vs. 54% and 33% of the quiescent UC patients reported abdominal pain (both p ≤ 0.02). In the longitudinal cohort, 71% had abdominal pain at diagnosis vs. 46% when in remission (p < 0.001). In multivariable models, symptoms of anxiety were associated with higher abdominal pain levels in both cross-sectional cohorts (OR 1.75 [IQR 1.11-2.76] and OR 1.99 [1.45-2.73]), whereas in cohort II, active disease (OR 2.68 [1.61-4.45]) and female sex (OR 2.03 [1.21-3.41]) were also associated with pain. QoL was negatively correlated with higher levels of abdominal pain, both in active and quiescent disease., Conclusions: Abdominal pain in UC is prevalent and associated with lower QoL in both active and quiescent disease. Associated factors are active disease, female sex and psychological symptoms, especially anxiety. We suggest considering a holistic approach when treating UC patients with abdominal pain., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by discomfort with constipation and/or diarrhea with unclear pathophysiology. We aimed to determine the activities of colorectal eosinophils, neutrophils and epithelial cells by biomarkers in feces reflecting these activities., Methods: Fecal samples were collected from 185 patients with IBS before and after 8 weeks of placebo or mesalazine treatment and from 40 healthy subjects. Calprotectin, eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL) (pab/765) or dimer, human phospholipase BII-precursor (HPLBII-P) and myeloperoxidase (MPO) were measured by ELISA. Symptom scores were evaluated by diaries., Results: HPLBII-P, HNL (pab/765) and EDN, proteins secreted by intestinal epithelial cells, were elevated in IBS patients as compared to healthy subjects (p < 0.0001-p = 0.008). In contrast, the neutrophil proteins calprotectin, MPO and HNL dimer were unaltered. The eosinophilic protein ECP was lower in IBS (p = 0.001). HNL (pab/765) (p = 0.01) and EDN (p = 0.004) increased in IBS patients after mesalazine treatment. Colo-rectal mucosa showed strong staining of HPLBII-P and western blotting of fecal extracts showed the presence of mainly monomeric, epithelial-associated HNL., Conclusions: The absence of signs of involvement of neutrophils and eosinophils in IBS suggests that activity of local epithelial cells rather than inflammation may be a major determinant of the disease. The measurements of EDN, HNL (pab/765), and HPLBII-P may serve as potential fecal biomarkers in the study and monitoring of IBS., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Introduction: Patients with irritable bowel syndrome (IBS) often attribute the onset or worsening of gastrointestinal symptoms to intake of food. Hence, to alleviate symptoms, patients with IBS may avoid triggering foods, potentially impacting their dietary intake and diet quality. This study aimed to compare the habitual diet intake and quality of patients with IBS with controls and to explore the association between dietary habits and symptoms in patients with IBS., Methods: Patients with IBS were included in 4 clinical studies reporting habitual dietary intakes at baseline. Age- and sex-matched controls representing the general population were derived from the Swedish population-based Riksmaten study. Dietary intakes were assessed using 4-day food diaries. Diet quality was measured using the diet quality index-Swedish national dietary guidelines (DQI-SNR), and diet diversity was scored based on the variety of food groups consumed., Results: The study included 646 patients with IBS and 646 controls (38 ± 14 years, 77% female). Both groups adhered to Nordic nutrition recommendations for macronutrients, except patients consumed fewer carbohydrates. Patients reported eating less carbohydrates, coffee, and dairy products and more fats, lactose-free dairy products, and nuts and seeds compared with controls. Fewer patients had a good diet quality according to the DQI-SNR. In patients, symptom severity and gastrointestinal-specific anxiety were associated with reduced energy and carbohydrate intake, lower diet diversity, and worse diet quality. Poor diet quality was associated with younger age, more severe IBS symptoms, anxiety, and depression., Discussion: Patients with IBS exhibit different dietary patterns compared with controls, with poorer dietary habits linked to more severe symptoms. Understanding food-symptom associations may enhance the optimization and personalization of dietary management for patients with IBS., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut ® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients ( n = 6), UC patients with active disease ( n = 6), and healthy subjects (HS) ( n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions.

Background and Aims: Psychological symptoms are associated with poorer ulcerative colitis [UC]-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life [HRQoL], and to disentangle the directionality of effects between GI symptom levels and psychological distress., Methods: Self-reported gastrointestinal [GI] symptom severity, HRQoL, inflammatory biomarkers, and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity., Results: Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhoea and abdominal pain. Conversely, patients with lower initial levels of diarrhoea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhoea and abdominal pain preceded reductions in psychological symptoms over time., Conclusions: Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Patients with organic gastrointestinal (GI) diseases and diabetes mellitus (DM) can have concomitant disorders of gut-brain interaction (DGBI)., Objective: This study aimed to compare the global prevalence of DGBI-compatible symptom profiles in adults with and without self-reported organic GI diseases or DM., Methods: Data were collected in a population-based internet survey in 26 countries, the Rome Foundation Global Epidemiology Study (n = 54,127). Individuals were asked if they had been diagnosed by a doctor with gastroesophageal reflux disease, peptic ulcer, coeliac disease, inflammatory bowel disease (IBD), diverticulitis, GI cancer or DM. Individuals not reporting the organic diagnosis of interest were included in the reference group. DGBI-compatible symptom profiles were based on Rome IV diagnostic questions. Odds ratios (ORs [95% confidence interval]) were calculated using mixed logistic regression models., Results: Having one of the investigated organic GI diseases was linked to having any DGBI-compatible symptom profile ranging from OR 1.64 [1.33, 2.02] in GI cancer to OR 3.22 [2.80, 3.69] in IBD. Those associations were stronger than for DM, OR 1.26 [1.18, 1.35]. Strong links between organic GI diseases and DGBI-compatible symptom profiles were seen for corresponding (e.g., IBD and bowel DGBI) and non-corresponding (e.g., IBD and esophageal DGBI) anatomical regions. The strongest link was seen between fecal incontinence and coeliac disease, OR 6.94 [4.95, 9.73]. After adjusting for confounding factors, associations diminished, but persisted., Conclusion: DGBI-compatible symptom profiles are more common in individuals with self-reported organic GI diseases and DM compared to the general population. The presence of these concomitant DGBIs should be considered in the management of organic (GI) diseases., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)