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Abstract Background Irritable bowel syndrome (IBS) is a common disease with unknown etiology. Poor dietary intake with nutritional deficiency and overweight have been described to increase the risk of IBS. The aim of the present study was to compare weight and circulating levels of micronutrients in IBS compared with healthy controls. Design Cross-sectional study. Methods Patients diagnosed with IBS and healthy volunteers were recruited. Participants had to complete a dietary diary book and the questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). Weight and height were measured, and blood samples were drawn. C-reactive protein (CRP), cobalamin, folate, iron, total iron-binding capacity (TIBC), and 25-hydroxy (25-OH) vitamin D were analyzed. Differences were calculated between groups and generalized linear model for regressions was adjusted for false discovery rate (FDR). Results IBS patients (n = 260) were elder than controls (n = 50) (44.00 (33.25-56.00) vs. 37.85 (30.18–45.48) years; p = 0.012). After adjustment for age, both weight (β: 5.880; 95% CI: 1.433–10.327; p = 0.010, FDR = 0.020) and body mass index (BMI) (β: 2.02; 95% CI: 0.68–3.36; p = 0.003, FDR = 0.012) were higher in patients. Among IBS participants, 48.1% were overweight/obese compared with 26.0% in controls (p = 0.007). Diarrhea-predominated IBS had highest weight (p

Abstract Background In the European Union alone, more than 100 million people present to the emergency department (ED) each year, and this has increased steadily year-on-year by 2–3%. Better patient management decisions have the potential to reduce ED crowding, the number of diagnostic tests, the use of inpatient beds, and healthcare costs. Methods We have established the Skåne Emergency Medicine (SEM) cohort for developing clinical decision support systems (CDSS) based on artificial intelligence or machine learning as well as traditional statistical methods. The SEM cohort consists of 325 539 unselected unique patients with 630 275 visits from January 1st, 2017 to December 31st, 2018 at eight EDs in the region Skåne in southern Sweden. Data on sociodemographics, previous diseases and current medication are available for each ED patient visit, as well as their chief complaint, test results, disposition and the outcome in the form of subsequent diagnoses, treatments, healthcare costs and mortality within a follow-up period of at least 30 days, and up to 3 years. Discussion The SEM cohort provides a platform for CDSS research, and we welcome collaboration. In addition, SEM’s large amount of real-world patient data with almost complete short-term follow-up will allow research in epidemiology, patient management, diagnostics, prognostics, ED crowding, resource allocation, and social medicine.

Abstract Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.

Abstract The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children

Abstract Background Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. Methods Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. Results MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020–17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042–1.506; p = 0.058). Conclusion Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.

Abstract Background Medical student master’s theses are often carried out as research projects, and some are published as research papers in journals. We investigated the percentage of master’s theses conducted by 5th -year students at the Medical Degree Program at Lund University, Sweden, that subsequently served as the basis for research publications. In addition, we explored both student and supervisor experiences with the publishing process. Methods A cohort of four semesters of student data covering the period from 2019 to 2020 (n = 446) was searched in PubMed, Embase and the Web of Science to assess whether they had been published as research papers. Surveys were sent to students (n = 121) and supervisors (n = 77) to explore their experiences with the publishing process. Results We found that 33% (149 of 446) of the students in the 2019–2020 cohort subsequently published their theses, and 50% of these students were listed as first authors. Most students published original research. Students (n = 21) and supervisors (n = 44) reported that the publishing process was time-consuming and that students needed multilevel support from supervisors to achieve successful publication. The publishing process was reported by 79% of the students to have led to additional learning. Most of the papers (126 of 149, 85%) had a clinical or patient-oriented focus. Conclusion A high percentage of the student publications in which students are listed as first authors require engagement from both students and supervisors. Supervisors play an essential role in supporting students in a successful publication process. Most of the published papers were either clinical or patient-oriented research.

Background Irritable bowel syndrome (IBS) is common with a global prevalence of 4%. Dietary regimes with a low content of fermentable oligo-, di-, and monosaccharides and polyol (FODMAP) or a starch- and sucrose-reduced diet (SSRD) have proven to be efficient. The aim of the present study was to describe the recruitment process for a randomized dietary trial with low FODMAP or SSRD for 4 weeks with a follow-up period of 5 months. The results of the dietary trial itself are not included in this paper but will be presented in another publication. Methods The County of Skåne, with 1,41 million inhabitants, was used as a base to perform a dietary trial in which IBS patients, age 18-70 years, were randomized to either low FODMAP or SSRD for 4 weeks. The estimated number of IBS patients in the actual age span was approximately 32,000. The trial was announced through lectures, letters to all primary healthcare centers (n=203), social media (two campaigns), and invitations to IBS patients identified in medical records (n=744). Results Three referrals arrived from the healthcare system, 17 patients contacted the investigators in person after receiving information from their healthcare center, and four patients contacted the investigators after recommendations from friends. Of these, 14 were enrolled in the study. From social media, 218 names were delivered, of which 93 fulfilled the study criteria and were willing to participate when contacted by the investigators (42.7%). Of the 3587 identified IBS patients in medical records in close proximity to the hospital, 744 were randomly contacted. Forty-eight patients (6.5 %) were willing to be included in the study. Thus, 155 patients with IBS were included in this study. Conclusions The inclusion rate for dietary intervention was very low considering the large population informed about the study. Announcements on social media seem to be the best way to recruit patients for intervention. Trial registration NCT05192603, 29/11/2021, ClinicalTrials.gov. The PRS URL is https://register.clinicaltrials.gov

A diet with low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) is established treatment for irritable bowel syndrome (IBS), with well-documented efficiency. A starch- and sucrose-reduced diet (SSRD) has shown similar promising effects. The primary aim of this randomized, non-inferiority study was to test SSRD against low FODMAP and compare the responder rates (RR = ∆Total IBS-SSS ≥ −50) to a 4-week dietary intervention of either diet. Secondary aims were to estimate responders of ≥100 score and 50% reduction; effects on extraintestinal symptoms; saturation; sugar craving; anthropometric parameters; and blood pressure. 155 IBS patients were randomized to SSRD (n = 77) or low FODMAP (n = 78) for 4 weeks, with a follow-up 5 months later without food restrictions. The questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS) were completed at baseline and after 2 and 4 weeks and 6 months. Weight, height, waist circumference, and blood pressures were measured. Comparisons were made within the groups and between changes in the two groups. There were no differences between groups at baseline. The responder rate of SSRD was non-inferior compared with low FODMAPs at week 2 (79.2% vs. 73.1%; p = 0.661;95% confidence interval (CI) = −20–7.2) and week 4 (79.2% vs. 78.2%; p = 1.000;95%CI = −14–12). Responder rate was still high when defined stricter. All gastrointestinal and extraintestinal symptoms were equally improved (p < 0.001 in most variables). SSRD rendered greater reductions in weight (p = 0.006), body mass index (BMI) (p = 0.005), and sugar craving (p = 0.05), whereas waist circumference and blood pressure were equally decreased. Weight and BMI were regained at follow-up. In the SSRD group, responders at 6 months still had lowered weight (−0.7 (−2.5–0.1) vs. 0.2 (−0.7–2.2) kg; p = 0.005) and BMI (−0.25 (−0.85–0.03) vs. 0.07 (−0.35–0.77) kg/m2; p = 0.009) compared with baseline in contrast to non-responders. Those who had tested both diets preferred SSRD (p = 0.032). In conclusion, a 4-week SSRD intervention was non-inferior to low FODMAP regarding responder rates of gastrointestinal IBS symptoms. Furthermore, strong reductions of extraintestinal symptoms were found in both groups, whereas reductions in weight, BMI, and sugar craving were most pronounced following SSRD.

Elevated levels of glial fibrillary acidic protein (GFAP) in plasma reflect neuroinflammation and are linked to cognitive decline. Preclinical studies show that dietary change can attenuate astrocyte reactivity and neuroinflammation. In the current study, we investigate if the Okinawa-based Nordic (O-BN) diet alters plasma GFAP levels in patients with Type 2 Diabetes (T2D), a metabolic disorder associated with cognitive disturbances and an increased risk of dementia. Plasma GFAP levels were measured in T2D patients (n = 30) at baseline, after 3 months of the diet, and after a subsequent 4 months of unrestricted diets. The GFAP levels decreased significantly after 3 months of the diet (p = 0.048) but reverted to baseline levels after 4 months of unrestricted diets. At baseline, the GFAP levels correlated significantly with levels of the neurodegeneration marker neurofilament light polypeptide (r = 0.400*) and, after correcting for age, sex, and body mass index, with proinflammatory plasma cytokines (ranging from r = 0.440* to r = 0.530**) and the metabolic hormone islet amyloid polypeptide (r = 0.478*). We found no correlation with psychological well-being. These results suggest that the O-BN diet reduces neuroinflammation in T2D patients and may thus be an important preventive measure for managing T2D and reducing the risk of neurodegenerative disorders.

Pancreas-derived islet amyloid polypeptide (IAPP) aggregates and deposits in the pancreas and periphery of Type 2 Diabetes (T2D) patients, contributing to diabetic complications. The excess IAPP can be removed by autoantibodies, and increased levels of immunoglobulin (Ig) G against IAPP have been reported in T2D patients. However, whether other Ig classes are also affected and if the levels can be managed is less known. This pre–post study examines IgA levels against IAPP oligomers (IAPPO-IgA) in T2D patients and assesses the impact of the Okinawa-based Nordic (O-BN) diet—a low-carbohydrate, high-fiber diet—on these levels after following the diet for 3 months. IAPP, IAPPO-IgA, and total IgA levels were measured in plasma and fecal samples from n = 30 T2D patients collected at baseline, after 3 months of diet, and after additional 4 months of unrestricted diets (a clinical follow-up). The IAPP and IAPPO-IgA levels were significantly lower after 3 months, with the latter also being significantly reduced at the clinical follow-up. The reduction in plasma IAPP and IAPPO-IgA levels correlated with reductions in plasma levels of metabolic and inflammatory markers. Hence, following the O-BN diet for at least 3 months is sufficient to reduce circulating IAPP and IAPPO-IgA levels, which may be principal in managing T2D.

Gastrointestinal (GI) symptoms are common in postural orthostatic tachycardia syndrome (POTS). We aimed to explore the prevalence and severity of GI symptoms in POTS, and to investigate immunological factors, hemodynamic findings, and their possible association with GI symptoms in POTS. Forty-three patients (93% female, median age 30.6 (26.0–41.0) years), previously diagnosed with POTS and 74 healthy controls (78% female, median age 35.6 (28.8–41.7) years) were included. The participants completed a questionnaire including prevalence of GI symptoms, the irritable bowel syndrome severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). All POTS patients were previously examined by tilt test (2010–2021) and the vast majority with more recent active standing test (2017–2021), which included monitoring of heart rate (HR). ΔHR was calculated as difference between supine and upright position. Continuous variables from IBS-SSS and VAS-IBS were correlated to ΔHR. A microarray containing several autoantigens commonly targeted in systemic autoimmune disorders was used to assess prevalent autoantibodies in POTS and controls. Total IgE and S-tryptase were analyzed. GI symptoms were more prevalent and severe in POTS than in controls; nausea being the most prevalent (79.1% vs 4.9%, p < 0.001) and bloating and flatulence being the most severe (median 65 (25–88) vs 0 (0–14), p < 0.001). The median total IBS-SSS was 213 (135–319) in POTS vs 13 (0–54) in controls (p < 0.001). Total IBS-SSS was associated with low psychological wellbeing (r = 0.539, p < 0.001) in POTS. ΔHRmax correlated inversely with abdominal pain (r = −0.406, p = 0.007). After adjustments for psychological wellbeing, total IBS-SSS still associated inversely with ΔHR10min (β: 4.748; 95% CI: −9.172 to −0.324; p = 0.036). Similar results were seen with active standing test. The prevalence of autoantibodies did not differ between POTS and controls (29.4% vs 33.3%, p = 0.803). There was no association between GI symptoms and autoantibody status. Total IgE and tryptase were elevated in a few cases. This study confirms the high prevalence of GI symptoms in POTS. More pronounced tachycardia upon tilt table testing seems to be inversely correlated with severity of chronic GI symptoms in POTS. This study did not support the hypothesis that POTS is associated with immunological factors.

Abstract Background Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. Method The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups. Results Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06–3.26; p = 0.029), as well as with age 50–59 years (OR:6.92; 95%CI:1.97–24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56–25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08–5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19–7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14–4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02–3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14–2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98–1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03–1.89; p = 0.033) and inversely with age 50–59 years (OR:0.58; 95%CI:0.38–0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants. Conclusion There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.

Microscopic colitis (MC) is classified as collagenous colitis (CC) and lymphocytic colitis (LC). Genetic associations between CC and human leucocyte antigens (HLAs) have been found, with smoking being a predisposing external factor. Smoking has a great impact on metabolomics. The aim of this explorative study was to analyze global metabolomics in MC and to examine whether the metabolomic profile differed regarding the type and course of MC, the presence of IBS-like symptoms, treatment, and smoking habits. Of the 240 identified women with MC aged ≤73 years, 131 completed the study questionnaire; the Rome III questionnaire; and the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS). Blood samples were analyzed by ultra-high-performance liquid chromatograph mass spectrometry (UHLC-MS/UHPLC-MSMS). The women, 63.1 (58.7–67.2) years old, were categorized based on CC (n = 76) and LC (n = 55); one episode or refractory MC; IBS-like symptoms or not; use of corticosteroids or not; and smoking habits. The only metabolomic differences found in the univariate model after adjustment for false discovery rate (FDR) were between smokers and non-smokers. Serotonin was markedly increased in smokers (p < 0.001). No clear patterns appeared when conducting a principal component analysis (PCA). No differences in the metabolomic profile were found depending on the type or clinical course of the disease, neither in the whole MC group nor in the subgroup analysis of CC.

Abstract Background Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease. Methods Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed. Results Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins. Conclusion The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.

Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1–V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism.

Objective The studies of early life factors and development of functional bowel diseases show inconsistent results. We therefore examined associations between certain early life factors and functional bowel symptoms in adulthood. Design Population-based cross-sectional study. Setting Weight and height were measured and questionnaires were completed at the time point of enrollment in MOS. Subjects 1013 participants in the Malmö Offspring Study (MOS) without organic bowel disease with data available from the Swedish Medical Birth Registry. Main outcome measures Associations were calculated between gestational age, birth weight, small-for-gestational-age and Apgar score from the Birth Registry, and symptoms according to the visual analog scale for irritable bowel syndrome (VAS-IBS) (abdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea, and symptoms’ influence on daily life) or self-reported IBS using logistic regression. Results In all, 253 (25.0%) participants reported bowel symptoms during the past 2 weeks and 179 (17.7%) self-reported IBS; conditions which were strongly associated (p

Abstract Objective The present population-based study aimed to examine the association of chronic stress and sleeping difficulties with self-reported irritable bowel syndrome (IBS), gastrointestinal (GI) symptoms past 2 weeks, and psychological well-being. Results The Malmö Offspring Study included subjects from the general population to complete a questionnaire regarding sociodemographic factors, lifestyle factors, and medical health. Experience of chronic stress during the past or past 5 years was reported. Sleeping patterns included sleeping quality, sleeping hours per day, sleeping onset difficulties, and wake-up frequency. The severity of GI symptoms was measured with the visual analog scale for IBS. Associations of stress and sleeping habits with IBS and GI symptoms were calculated by logistic regression and generalized linear model, adjusted for sociodemographic and lifestyle factors. After exclusion of organic GI disorders or missing values, 2648 participants remained. Participants with self-reported IBS (n = 316) and GI symptoms (n = 459) were often women and smokers. After full adjustment, chronic stress past year was associated with GI symptoms (OR: 1.347; 95% CI 1.030–1.762), whereas stress past 5 years (OR: 1.415; 95% CI 1.058–1.892) and sleeping onset difficulties ≥ 3 times weekly (OR: 2.153: 95% CI 1.228–3.774) were associated with IBS. Stress, poor sleeping quality, sleeping onset difficulties, and IBS/GI symptoms were all associated with poor psychological well-being (p

Background: Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits. Further, IBS patients experience a high degree of extraintestinal symptoms. Objectives: The aim of this review was to describe the relation between IBS and extraintestinal manifestations and mechanisms and treatments of these extraintestinal manifestations. Design: The study was performed as a systematic review. Data Sources and Methods: Search terms including extraintestinal manifestations or somatization and IBS were used to scrutinize for publications in Pubmed. In total, 630 publications were identified and 80 were finally included in this review. Results: About 50% of all IBS patients have extraintestinal manifestations in addition to gastrointestinal symptoms. Somatic pain, fatigue, and sleeping disturbances are most common, and most often described in women. Both extraintestinal manifestations and psychological distress are associated with exaggerated gastrointestinal symptoms, impaired quality of life, and difficulties to treat IBS symptoms. The extraintestinal manifestations render an excess of healthcare costs. Varying etiology and pathophysiology to IBS are discussed, and many patients express a general hypersensitivity. Extraintestinal symptoms are seldom documented at clinical healthcare or included in the assessment of treatment outcomes. A good patient-physician relationship and strengthening of coping mechanisms have rendered less gastrointestinal symptoms, psychological distress, and somatization. Altered lifestyle habits may improve both gastrointestinal and extraintestinal symptoms. Pharmacological treatment, including antidepressant drugs, should be considered when lifestyle advice fails. Teamwork between different specialists and healthcare providers may be of importance in the wide range of symptoms and extraintestinal manifestations. Conclusion: Extraintestinal manifestations are common in IBS patients and is associated with worse suffering and difficulties to treat symptoms. Evaluation and treatment of IBS patients should consider also extraintestinal manifestations and their treatment outcome. Establishment of good relationship, strengthening of coping mechanisms, and education in healthier lifestyle habits are crucial in the management of these patients.

BackgroundThe pathogenesis of appendicitis is not understood completely and establishing a correct diagnosis can be clinically challenging. Previous investigations have shown an association between a T helper cell (Th)2-mediated inflammatory response, for example immunoglobulin E (IgE)-mediated allergy, and a decreased risk of complicated appendicitis. The present study aimed to evaluate differences in serum concentrations of IgE and Th2-associated interleukins (IL) in children with uncomplicated and complicated appendicitis.MethodA prospective study including children

Abstract Neuropathy should be considered as a possible etiological factor in patients with severe gastrointestinal symptoms, without signs of disease on routine investigations. Examinations of the autonomic and peripheral nervous systems may be helpful to select the patients who should be investigated with full‐thickness intestinal biopsy, and to give appropriate care.

Background: The influence of daily life exposure on the gastrointestinal tract is not fully understood. This study aimed to examine associations between functional gastrointestinal symptoms and sociodemographic status and lifestyle habits in the general population.Methods: The Malmö Offspring Study (MOS) included 2,648 participants from the general population who had answered a questionnaire about sociodemographic status, lifestyle habits, medical health, and self-reported irritable bowel syndrome (IBS). The visual analog scale for IBS (VAS-IBS) was completed to assess gastrointestinal symptoms the past 2 weeks. Subjects with organic gastrointestinal diseases were excluded. Presence of self-reported IBS and gastrointestinal symptoms the past 2 weeks were used as dependent variables to study the associations with age, sex, body mass index, education, occupation, marital status, smoking, snuff using, alcohol drinking frequency, alcohol amount per drinking occasion, physical activity at work, and physical activity during leisure time, using logistic regression and generalized linear model.Results: Self-reported IBS was associated with gastrointestinal symptoms the past 2 weeks (p < 0.001). There was an association between IBS and female sex (p < 0.001), former smoking (p < 0.001), present smoking (p < 0.001), and an inverse association with drinking 3–4 standard glasses per occasion (p = 0.038). Gastrointestinal symptoms were associated with age 50–59 years (p = 0.009), ≥60 years (p = 0.004), female sex (p < 0.001), studying (p = 0.036), unemployment (p = 0.009), former smoking (p = 0.001), and present smoking (p = 0.012). In men, IBS was associated with middle-age and both IBS and gastrointestinal symptoms were associated with unemployment (p < 0.001 and p = 0.001, respectively). In women, IBS was associated with present smoking (p = 0.022), and gastrointestinal symptoms were associated with former smoking and inversely associated with higher age (p = 0.006) and intermediate physical activity at work (p = 0.008). No associations were found with BMI, education, marital status, or snuff using.Conclusion: Self-reported IBS in the general population shows strongest association with female sex and smoking, whereas gastrointestinal symptoms also are associated with unemployment and inversely associated with higher age. In men, both IBS and gastrointestinal symptoms are associated with unemployment. In women, both IBS and gastrointestinal symptoms are associated with smoking, whereas symptoms are inversely associated with higher age and intermediate physical activity.

Irritable bowel syndrome (IBS) is characterized by gastrointestinal symptoms. Overweight and increased risk of metabolic syndromes/diabetes are observed in IBS, conditions associated with plasminogen activator inhibitor-1 (PAI-1) and visfatin. The aim of this study was to measure blood levels of AXIN1, cholecystokinin (CCK), enkephalin, ghrelin, neuropeptide Y (NPY), PAI-1, and visfatin before and after a 4-week intervention with a starch- and sucrose-reduced diet (SSRD). A total of 105 IBS patients were randomized to either SSRD (n = 80) or ordinary diet (n = 25). Questionnaires were completed, and blood was analyzed for AXIN1 and hormones. AXIN1 (p = 0.001) and active ghrelin levels (p = 0.025) were lower in IBS than in healthy volunteers at baseline, whereas CCK and enkephalin levels were higher (p < 0.001). In the intervention group, total IBS-symptom severity score (IBS-SSS), specific gastrointestinal symptoms, psychological well-being, and the influence of intestinal symptoms on daily life were improved during the study, and weight decreased (p < 0.001 for all), whereas only constipation (p = 0.045) and bloating (p = 0.001) were improved in the control group. PAI-1 levels tended to be decreased in the intervention group (p = 0.066), with a difference in the decrease between groups (p = 0.022). Visfatin levels were decreased in the intervention group (p = 0.007). There were few correlations between hormonal levels and symptoms. Thus, this diet not only improves IBS symptoms but also seems to have a general health-promoting effect.

There is increasing evidence suggesting a role of intestinal dysfunction in a number of autoimmune diseases. Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with a documented increased level of intestinal inflammation, whereas multiple sclerosis (MS) is an organ-specific autoimmune disease known to exhibit increased intestinal permeability. In this study we determine to what extent intestinal inflammation, analysed by a faecal calprotectin ELISA, is accompanied by altered intestinal wall permeability, as measured by a lactulose and mannitol intestinal absorption assay. Intestinal permeability was increased in both pSS and MS patients, while faecal calprotectin was elevated in pSS but normal in MS. Our findings suggest different mechanisms mediating a leaky gut in these two diseases: in pSS there is autoimmune attack directly on the intestinal wall; in MS, with autoimmunity being limited to the CNS, it may be due to a disturbed CNS regulation of enteric nerve function.

For a whole century, citrate has been used as an in vitro anticoagulant via chelation of calcium. Later, also EDTA was introduced as an anticoagulant. An often overlooked fact is that zinc is bound to citrate and EDTA with affinities much greater than that for calcium, imposing problems in biomedical research. In vivo, proteins of the S100 family are released from leukocytes and known to bind calcium. Some of them, e.g., calprotectin, also chelate zinc. Thus, at an inflamed site, the ratio between Ca2+ and Zn2+ is changed. This mechanism is of importance for the modulation of the activation of a fascinating family of post-translationally acting calcium-dependent thiol enzymes, the transglutaminases, which are inhibited by zinc. This presentation illustrates the complexity of in vitro studies with zinc. Moreover, it exemplifies the role of Zn2+ in pathophysiological situations such as celiac disease and neurodegeneration.

Sociodemographic factors and lifestyle habits affect body weight and body composition. A new syndrome, called normal-weight obesity (NWO), is found in individuals with normal weight and excess body fat in contrast to lean and overweight individuals. The aim of the present study was to explore the associations between sociodemographic factors and smoking and alcohol habits and lower versus higher BMI (≥25 kg/m2) and to examine whether categorization into lean, NWO, and overweight leads to further information about sociodemographic and lifestyle associations, compared with the common categorization defined by BMI. A cohort of 17,724 participants (9,936 females, 56.1%) from the EpiHealth study, with a median age of 61 (53–67) years, was examined. The participants answered a questionnaire about lifestyle, and weight and fat percentage were measured. Associations between sociodemographic factors and lifestyle habits and lower versus higher BMI, and lean versus NWO or lean and NWO versus overweight were calculated by binary logistic regression. Male sex, age, sick leave/disability, married/cohabitating, divorced/widowed, former smoking, and a high alcohol consumption were associated with higher BMI, whereas higher education and frequent alcohol consumption were inversely associated (all p

Background: An Okinawa-based Nordic diet with moderately low carbohydrate content and high fat and protein content has been shown to improve anthropometry and metabolism in type 2 diabetes. Objective: The objectives of this study were to measure plasma or serum levels of hormones regulating energy metabolism and metabolic control, that is, cholecystokinin (CCK), Cortisol, C-peptide, ghrelin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), polypeptide YY (PYY), resistin, and visfatin after this diet intervention, and to determine partial correlations between hormonal levels and anthropometric and metabolic responses. Design: A total of 30 patients (17 women) with type 2 diabetes, mean age 57.5 ± 8.2 years, and body mass index (BMI) 29.9 ± 4.1 kg/m2 were served the diet for 12 weeks. Fasting hormones were measured by Luminex and enzyme–linked immunosorbent assay (ELISA) before study start and after 12 and 28 weeks, along with anthropometric and metabolic parameters. Result: The levels of CCK (P = 0.005), cortisol (P = 0.015), C-peptide (P = 0.022), glucagon (P = 0.003), GLP-1 (P = 0.013), GIP (P < 0.001), insulin (P = 0.004), leptin (P < 0.001), and PYY (P < 0.001) were lowered after dietary intervention. These reduced levels only remained for PYY at week 28 (P = 0.002), when also ghrelin (P = 0.012) and visfatin (P = 0.021) levels were reduced. Changes of glucose values correlated with changed levels of C-peptide and PYY (P < 0.001), insulin (P = 0.002), and PAI-1 (P = 0.009); changes of triglyceride values with changed levels of C-peptide, insulin, and PYY (P < 0.001) and PAI-1 (P = 0.005); changes of insulin resistance with changes of leptin levels (P = 0.003); and changes of BMI values with changed levels of C-peptide, insulin, and leptin (P < 0.001). Conclusions: Okinawa-based Nordic diet in type 2 diabetes has significant impact on the endocrine profile, which correlates with anthropometric and metabolic improvements.

A full-thickness biopsy of the bowel wall is required to evaluate the enteric nervous system. A patient with aggravating gastrointestinal symptoms underwent a laparoscopic full-thickness biopsy of the ileum and, 1 year later, an endoscopic full-thickness biopsy of the sigmoid colon. Both samples showed enteric neuropathy characterized by vacuolated and enlarged neurons. The length of the myenteric plexus was greater in the endoscopic (23 mm) compared to the laparoscopic (11 mm) biopsy, with fewer tissue artefacts in the laparoscopic approach. Clinical deterioration was paralleled by enteric neuropathy with an increase in the percentage of vacuolated and enlarged enteric neurons from 24 to 35%.

Abstract Background High levels of blood glucose are thought to be associated with colorectal cancer (CRC) and hyperinsulinemia, an interstage in the development of CRC. The purpose of this study was to examine associations between incident CRC and blood glucose; plasma insulin; and the homeostasis model assessment for insulin resistance (HOMA2-IR), respectively, and to determine whether these associations were dependent on sex and cancer site. Methods The Malmö Diet and Cancer cardiovascular cohort comprises 6103 individuals. During 81,781 person-years of follow-up, 145 cases of CRC were identified. The hazard ratio of measured blood glucose and plasma insulin and calculated HOMA2-IR were estimated with Cox proportional hazard regression. Results An association was found between high levels of blood glucose and risk of CRC (HR: 1.72 for the highest compared with the lowest quartile; 95% CI: 1.05, 2.84; ptrend = 0.044), and colon cancer (HR: 1.70 for the highest compared with the lowest quartile; 95% CI: 0.87, 3.33; ptrend = 0.032). In men, an association was found between blood glucose and CRC (HR: 2.80 for the highest compared with the lowest quartile; 95% CI: 1.37, 5.70; ptrend = 0.001), and colon cancer (HR: 4.48 for the highest compared with the lowest quartile; 95% CI: 1.27, 15.84; ptrend = 0.007), but this was not found in women. No associations between plasma insulin, or HOMA2-IR, and CRC, were found. Conclusion High levels of blood glucose in men are associated with risk of colon cancer. The findings contribute to facilitating to identify those most in need of prevention and screening.

Abstract Background Altered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases including primary Sjögren’s syndrome (pSS). The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis. Methods Forty-two consecutive pSS patients and 35 age-matched and sex-matched control subjects were included in the study in an open clinic setting. Stool samples were analyzed for intestinal dysbiosis using a validated 16S rRNA-based microbiota test (GA-map™ Dysbiosis Test; Genetic Analysis, Oslo, Norway). Dysbiosis and severe dysbiosis were defined in accordance with the manufacturer’s instructions. Patients were evaluated with regard to disease activity (European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and Clinical ESSDAI (ClinESSDAI)). In addition, patients were examined for laboratory and serological features of pSS as well as fecal calprotectin levels. Furthermore, patients were investigated regarding patient-reported outcomes for pSS (EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI)) and irritable bowel syndrome (IBS)-like symptoms according to the Rome III criteria. Results Severe dysbiosis was more prevalent in pSS patients in comparison to controls (21 vs 3%; p = 0.018). Subjects with pSS and severe dysbiosis had higher disease activity as evaluated by the ESSDAI total score (13 vs 5; p = 0.049) and the ClinESSDAI total score (12 vs 5; p = 0.049), lower levels of complement component 4 (0.11 vs 0.17 g/L; p = 0.004), as well as higher levels of fecal calprotectin (110 vs 33 μg/g; p = 0.001) compared to the other pSS patients. In contrast, severe dysbiosis among pSS patients was not associated with disease duration, IBS-like symptoms, or the ESSPRI total score. Conclusions Severe intestinal dysbiosis is a prevalent finding in pSS and is associated both with clinical and laboratory markers of systemic disease activity as well as gastrointestinal inflammation. Further studies are warranted to elucidate a potential causative link between dysbiosis and pSS.

A 4-week dietary intervention with a starch- and sucrose-restricted diet (SSRD) was conducted in patients with irritable bowel syndrome (IBS) to examine the metabolic profile in relation to nutrient intake and gastrointestinal symptoms. IBS patients were randomized to SSRD intervention (n = 69) or control continuing with their ordinary food habits (n = 22). Food intake was registered and the questionnaires IBS-symptoms severity scale (IBS-SSS) and visual analog scale for IBS (VAS-IBS) were completed. Metabolomics untargeted analysis was performed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) in positive and negative ionization modes. SSRD led to marked changes in circulating metabolite concentrations at the group level, most prominent for reduced starch intake and increased polyunsaturated fat, with small changes in the control group. On an individual level, the correlations were weak. The marked reduction in gastrointestinal symptoms did not correlate with the metabolic changes. SSRD was observed by clear metabolic effects mainly related to linoleic acid metabolism, fatty acid biosynthesis, and beta-oxidation.

Abstract Background Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. Methods We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Results Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70–81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. Conclusions These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

Aim. Parkinson’s disease is often accompanied by gastrointestinal symptoms, especially constipation. Microscopic studies of the enteric nervous system and enteric neuropathy have often been performed by immunostaining in the myenteric plexa. The aim of the present study was to examine whether pathologic changes could be identified by conventional hematoxylin and eosin (H&E) staining and could also be seen in the submucosal plexa. Materials and Methods. In 20 deceased cases (11 male/9 female) of Parkinson’s disease, the intestinal tract was investigated for potential neuroganglionic disease. Ten cases (7 male/3 female) of non-Parkinson, intestinally asymptomatic individuals were used as controls. Specimens from the jejunum and colon were sampled. The material was treated with standard histopathological procedures, i.e., fixed in formaldehyde solution, dehydrated and embedded in paraffin, sectioned at 5 μm thickness, and stained with H&E and immunostaining for α-synuclein. Results. In 15 cases (7 male/8 female) of Parkinson’s disease, atrophic/pycnotic nerve plexus cells were present, i.e., signs of ganglionic degeneration in the submucosal and/or myenteric plexa, mostly identified in both loci, by H&E staining. In some cases, the degenerative signs were mild, however, corroborated by findings of α-synuclein deposits in the ganglion cells. The remaining 5 cases showed no signs of degeneration in the H&E staining, but immunostaining revealed minimal α-synuclein deposits in 3 cases. None of the controls showed any ganglionic degeneration/α-synuclein deposits. Conclusion. It seems possible to identify a morphologic intestinal disease substrate in Parkinson’s disease by H&E staining, showing ganglion cell pycnosis and degeneration in both plexa. This finding may indicate a potential to diagnose enteric neuropathy in highly accessible sites.

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, ‘abdominal pain’, ‘bloating/flatulence’ and ‘intestinal symptoms´ influence on daily life’ scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ −50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.

Background: Our hypothesis was that a modified diet would improve blood glucose control with beneficial impact on weight management and overall health in established diabetes. Objective: This prospective interventional study investigated the clinical effect of an Okinawan-based Nordic diet on anthropometry, metabolic control, and health-related quality of life (HRQoL) in Scandinavian type 2 diabetes patients. Design: Food was prepared and delivered to 30 type 2 diabetes patients. Clinical information along with data on HRQoL, blood samples, and urine samples were collected during 12 weeks of diet interventions, with follow-up 16 weeks after diet completion. Results: After 12 weeks of dietary intervention, a reduction in body weight (7%) (p

Gastrointestinal complaints without obvious organic causes confirmed by clinical laboratory analyses, endoscopy or radiology are often referred to functional entities. Irritable bowel syndrome (IBS) is the most common functional disorder in the gut. Careful examination of these patients may reveal other diagnoses of defined etiologies, e.g., enteric neuropathy, microscopic colitis, and primary Sjögre’s syndrome. The present case describes a young patient with incapacitating gastrointestinal symptoms presumed to be IBS, who underwent endoscopic full-thickness biopsy in sigmoid colon. Histopathological examination revealed degenerative enteric neuropathy, possibly secondary to chronic ischemia.

Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone, and luteinizing hormone orchestrate the reproduction cycle and regulate the sex steroid secretion from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neurotransmitters/peptides in various tissues, where the peptides exert many different effects. mRNA coding for GnRH1 and GnRH2 have been described in the human gastrointestinal tract, and GnRH has been found in both submucosal and myenteric neurons. mRNA coding for GnRH and the fully expressed peptide have been found in rat enteric neurons by some researchers but not by others. mRNA coding for GnRH receptors, but not the fully expressed receptor, has been found in one rat study. GnRH influences gastrointestinal motility and secretion. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatment for in vitro fertilization. Reduced numbers of enteric neurons and IgM antibodies against GnRH and progonadoliberin-2 (precursor of GnRH2) have been observed after such treatment, with the clinical picture of gastrointestinal dysmotility. Similarly, a rat model of enteric neurodegeneration has been developed after administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, progonadoliberin-2, and GnRH receptors have been described in patients with signs and symptoms of gastrointestinal dysmotility and/or autonomic dysfunction, such as irritable bowel syndrome, enteric dysmotility, diabetes mellitus, and primary Sjögren’s syndrome. Thus, apart from regulation of reproduction and sex hormone secretion, GnRH also constitutes a part of enteric nervous system (ENS) and its functions during physiological and pathological conditions. This review aimed to describe the role of GnRH in the ENS.

Patients with irritable bowel syndrome (IBS) exhibit low-grade inflammation and increased gut permeability. Dietary sugar has been shown to contribute to low-grade inflammation and increased gut permeability, and to correlate with gastrointestinal (GI) symptoms. The aim of the present study was to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal (GI) and extra-intestinal symptoms in IBS. One hundred and five IBS patients (82 women, 46.06 ± 13.11 years), with irritable bowel syndrome-symptom severity scale (IBS-SSS) > 175, were randomized to SSRD for 4 weeks or continued ordinary eating habits. The visual analog scale for irritable bowel syndrome (VAS-IBS), IBS-SSS, and 4-day food diaries were collected at baseline and after 2 and 4 weeks. After the intervention, one-third of the patients did not fulfill the criteria for IBS/functional gastrointestinal disorder. Half of the participants changed from moderate/severe disease to no/mild disease according to IBS-SSS. Comparisons between the groups showed decreased weight and sweet cravings, and parallel decreases in total IBS-SSS and extra-intestinal IBS-SSS scores, in the intervention group compared to controls (p < 0.001 for all). When calculating separate extra-intestinal symptoms, belching (p = 0.001), muscle/joint pain (p = 0.029), urinary urgency (p = 0.017), and tiredness (p = 0.011) were decreased after introduction of SSRD compared to controls. In conclusion, SSRD improves both GI and extra-intestinal symptoms in IBS.

Dietary advice constitutes one of the first choices of treatment for irritable bowel syndrome (IBS). We have recognized an increased prevalence of sucrase-isomaltase (SI) gene variants in IBS patients, possibly rendering starch- and sucrose-intolerance. The aims were to examine participants’ dietary habits at baseline, to correlate habits with gastrointestinal (GI) symptoms and blood levels of minerals and vitamins, and to examine the effect of a starch- and sucrose-reduced diet (SSRD) on GI symptoms. In the study 105 IBS patients (82 women, 46.06 ± 13.11 years), irritable bowel syndrome-symptom severity scale (IBS-SSS)>175, were randomized to SSRD for 2 weeks or continued ordinary eating habits. Blood samples, visual analog scale for irritable bowel syndrome (VAS-IBS), IBS-SSS, and 4-day food diaries were collected at baseline and after 2 weeks. Patients with irregular dietary habits exhibited higher IBS-SSS than patients with regular habits (p = 0.029). Women already on a diet had lower ferritin levels than others (p = 0.029). The intervention led to 66.3% of patients being responders, with differences in the change of IBS-SSS (p < 0.001), abdominal pain (p = 0.001), diarrhea (p = 0.002), bloating and flatulence (p = 0.005), psychological well-being (p = 0.048), and intestinal symptoms’ influence on daily life (p < 0.001), compared to controls. Decreased intake of cereals and sweets/soft drinks correlated with decreased scores.

Although endometriosis is considered an inflammatory disease, no reliable diagnostic biomarkers exist for use in clinical practice. The aim was to investigate the inflammatory profile in endometriosis using an exploratory approach of inflammation-related proteins. Patients with laparoscopy-verified endometriosis (N = 172), women with microscopic colitis (N = 50), healthy controls (N = 31), and age-matched controls from the general population (N = 100) were enrolled and questionnaires regarding socioeconomic factors, lifestyle habits, and medical history were completed. Sera from patients and healthy controls were analyzed for 92 inflammatory biomarkers using Proximity Extension Assay technology (PEA). Plasma AXIN1 levels were analyzed in patients with endometriosis and controls from the general population by ELISA. General linear model adjusted for age, Mann–Whitney U-test, and principal component analysis (PCA) were used for statistical calculations. Serum levels of AXIN1 and ST1A1 were increased in endometriosis compared with MC (p < 0.001) and healthy controls (p = 0.001), whereas CXCL9 levels were decreased. Plasma levels of AXIN1 were elevated in endometriosis compared with age-matched controls from the general population (30.0 (17.0–38.0) pg/mL vs. 19.5 (15.0–28.0) pg/mL, p < 0.001). PCA analysis identified four clusters of proteins, where one cluster differed between endometriosis and controls, with strong correlations for AXIN1 and ST1A1. Plasma/serum AXIN1 is an interesting biomarker to be further evaluated in endometriosis.

Irritable bowel syndrome (IBS) is a functional bowel disorder by unknown aetiology. Several reviews are written about pharmacological and psychological treatment of the disease. Nevertheless, healthcare professionals consider these patients difficult to handle in daily practice. There is an uncertainty about how to measure symptoms and to evaluate the effect of any given treatment. In the absence of objective markers, professionals feel unsure of how to manage the condition and the patients do not feel that they are taken seriously. The development of the short, self-reported questionnaire, Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS), offers a practical guide to objective measurement of symptoms and effect of given treatments into numerical values in the daily practice.

BackgroundObesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.Methods and findingsThe association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of ConclusionsThese results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Our understanding of the physiology of digestion, absorption, secretion, and motility in the gastrointestinal tract has improved immensely. Today it is well established that the gross functions of the gastrointestinal tract depend on the coordination between the muscles, nerves and hormones. The enteric nervous system (ENS) is involved in most of the physiological and pathophysiological processes in the gastrointestinal tract. Therefore, clinical and experimental studies on the ENS provide the basis for a better understanding of the mechanisms involved in gastrointestinal disorders and promote the development of therapeutic options. This review outlines some of the current views on the role of the ENS and its related hormones in gastrointestinal motility.

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