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The anaerobic spirochete Brachyspira causes intestinal spirochetosis, characterized by the intimate attachment of bacterial cells to the colonic mucosa, potentially leading to symptoms such as diarrhea, abdominal pain, and weight loss. Despite the clinical significance of Brachyspira infections, the mechanism of the interaction between Brachyspira and the colon epithelium is not known. We characterized the molecular mechanism of the B. pilosicoli-epithelium interaction and its impact on the epithelial barrier during infection. Through a proteomics approach, we identified BPP43_05035 as a candidate B. pilosicoli surface protein that mediates bacterial attachment to cultured human colonic epithelial cells. The crystal structure of BPP43_05035 revealed a globular lipoprotein with a six-bladed beta-propeller domain. Blocking the native BPP43_05035 on B. pilosicoli, either with a specific antibody or via competitive inhibition, abrogated its binding to epithelial cells, which required cell surface-exposed N-glycans. Proximity labeling and interaction assays revealed that BPP43_05035 bound to tight junctions, thereby increasing the permeability of the epithelial monolayer. Extending our investigation to humans, we discovered a downregulation of tight junction and brush border genes in B. pilosicoli-infected patients carrying detectable levels of epithelium-bound BPP43_05035. Collectively, our findings identify BPP43_05035 as a B. pilosicoli adhesin that weakens the colonic epithelial barrier during infection.

Abstract Background Poor muscle function is associated with a negative prognosis in advanced liver disease but the impact in compensated chronic liver disease is unknown. Similar prognostic uncertainty applies to fatigue. We aimed to assess the prognostic value of muscle performance and fatigue in a cohort of patients with compensated chronic liver disease. Methods We followed 241 patients with compensated chronic liver disease included in a study between 2010 and 2014. Subjects were 52 ± 15 years (mean ± SD; 134 females). All subjects performed four muscle function tests: “Timed Up and Go” test, walking speed, handgrip strength, and standing heel-rises. Fatigue was evaluated by fatigue impact scale. Follow up data was acquired through hospital records and registries. Results During follow up of 6.75 ± 1.4 years, 13 patients died (5.5%) and 11 (4.5%) patients underwent liver transplantation. A timed up and go over 10 s was not significantly associated with a lower survival (Kaplan-Meier, log rank test p = 0.132), or with transplant free survival (p = 0.543), Fig. 3. It was also not specifically associated with liver related causes of death (p = 0.597). The other physical functioning tests and fatigue were not significantly associated with mortality or transplant-free survival (p > 0.05 for all) except for maximal walking speed (2.2 vs. 1.9 m/s, p = 0.007). Conclusions Our study suggests that muscle function and fatigue are not key prognostic factors in compensated chronic liver disease. However, further confirmation in future studies is needed.

Abstract Background Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. Methods We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. Results IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. Conclusions These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

Abstract Background Irritable Bowel Syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Earlier studies have shown that IBS can limit the ability to perform at work and lead to absenteeism. However, few studies focus on work life experiences based on patients’ narratives. The purpose of this study was to construct a theory for how persons with IBS maintain their work life. Methods A qualitative study was performed using constructivist grounded theory. Semi-structured interviews with 15 women and 8 men with IBS (26–64 years of age) were conducted. Fourteen participants worked full-time, six worked part-time and three were on sick leave. The interviews were transcribed verbatim and coded line-by-line, incident-by-incident and thereafter focused coding was done. From the data and codes, categories were generated. Finally, a core category was constructed explaining the process of maintaining work life when living with IBS. Results Balancing work life while being under threat of symptoms constituted of four categories, being prepared, restricting impact, reconciling and adjusting. Persons with IBS restricted the impact of IBS on work by using strategies and upholding daily routines and strived to being prepared by exerting control over work life. These ongoing processes served to limit the influence of IBS on work by symptoms being less intense, perceived as less frequent, or not as bothersome. Reconciling IBS with work life was understood as a successful outcome from being prepared and restricting impact but was also influenced by the individual’s outlook on life. Adjusting to other people at work interfered with the strategies of being prepared, restricting impact, and reconciling, leaving persons with IBS more susceptible to symptoms. Conclusions This study deepens the understanding of the work situation for persons with IBS. Health care professionals can use the results of this study in the dialogue with the patient discussing work ability and sick leave. The results imply that although balancing work life under threat of symptoms can be a struggle, there are strategies that persons with IBS and employers together can initiate and use to reduce impact on work on several different levels.

Abstract Background Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. Methods The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into “no,” “occasional,” and “frequent” meal-related abdominal pain groups based on 0%, 10–40%, and ≥50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. Results Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. Conclusion Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.

Abstract Background Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular. Method Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1–2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals. Results The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1–2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05). Conclusions This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders.

Abstract Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

Abstract Background While several studies have documented associations between dietary habits and microbiota composition and function in healthy individuals, no study explored these associations in patients with irritable bowel syndrome (IBS), and especially with symptoms. Methods Here, we used a novel approach that combined data from a 4-day food diary, integrated into a food tree, together with gut microbiota (shotgun metagenomic) for individuals with IBS (N = 149) and healthy controls (N = 52). Paired microbiota and food-based trees allowed us to detect new associations between subspecies and diet. Combining co-inertia analysis and linear regression models, exhaled gas levels and symptom severity could be predicted from metagenomic and dietary data. Results We showed that individuals with severe IBS are characterized by a higher intake of poorer-quality food items during their main meals. Our analysis suggested that covariations between gut microbiota at subspecies level and diet could be explained with IBS symptom severity, exhaled gas, glycan metabolism, and meat/plant ratio. We provided evidence that IBS severity is associated with altered gut microbiota hydrogen function in correlation with microbiota enzymes involved in animal carbohydrate metabolism. Conclusions Our study provides an unprecedented resolution of diet-microbiota-symptom interactions and ultimately guides new interventional studies that aim to identify gut microbiome-based nutritional recommendations for the management of gastrointestinal symptoms. Trial registration This trial was registered on the ClinicalTrials.gov, with the registration number NCT01252550 , on 3rd December 2010. Video abstract

Abstract Although incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease.

Abstract Background The role of the fecal microbiota composition for the postoperative disease course of patients with Crohn’s disease (CD) who have undergone ileocecal resection remains to be established. In this study, we investigated if the fecal microbiota composition, determined by a high throughput test quantifying a pre-selected set of bacteria, is associated with the postoperative disease course of CD patients. Methods Fecal samples were obtained from healthy subjects as well as from CD patients, 3–10 weeks and 1 year after ileocaecal resection. The fecal microbial composition was analyzed by Genetic Analysis GA-map Dysbiosis test, targeting ≥300 bacteria on different taxonomic levels. Postoperative disease status was assessed endoscopically according to Rutgeerts scoring system 1 year after surgery. Differences in fecal microbiota composition between groups were analyzed by multivariate factor analyses and cluster analysis. Microbial stability over time was determined using Bray-Curtis dissimilarity. Results One year after surgery, the fecal microbiota composition differed between CD patients (n = 21) and healthy subjects (n = 7). At this time point, the microbiota composition of CD patients was associated with disease course, clearly separating patients with disease relapse (n = 8) and patients in remission (n = 13). Further, the microbial within-patient stability was high during the first year after surgery, irrespective of disease course. Conclusion The fecal microbiota composition of CD patients, analyzed by GA-map Dysbiosis test, is subject to little variation over time, and may potentially be used as a non-invasive diagnostic tool for the postoperative disease course.

Introduction: Ulcerative colitis (UC) contributes to impaired health-related quality of life (HRQoL). Although disease activity is the most important factor, reduced HRQoL has been reported even in quiescent UC. We aimed to determine HRQoL, and identify predictors thereof, in patients with long-standing UC in remission. Methods: In total, 66 patients with inactive UC were included 10 years after the disease onset. Clinical assessment including rigid sigmoidoscopy was performed to ensure remission. Data on demographic, clinical, treatment-related, and psychological determinants of HRQoL were obtained with a structured interview and self-assessment questionnaires measuring gastrointestinal (GI) and psychological symptoms and fatigue. HRQoL was measured with the Short Form Health Survey (SF-36). Results: The SF-36 domains were comparable to the general Swedish population, except for Vitality, where UC patients scored lower. Gender, smoking, comorbidity, or disease phenotype had no impact on HRQoL. In contrast, corticosteroid use and sick leave during the previous year were independently associated with Physical Functioning and Bodily Pain domains of SF-36; persisting GI symptoms during remission with Bodily Pain; and fatigue with Role Physical, General Health and Vitality. For all other SF-36 domains reflecting mental HRQoL (Social Function, Role Emotional, Mental Health), only psychological distress contributed uniquely. Conclusions: Although overall HRQoL in long-standing UC in remission is comparable to the general population, previous disease activity as well as persisting GI symptoms, fatigue, and psychological distress are associated with a lower HRQoL among these patients. Improved HRQoL may allow for better UC patient health and reduced costs for health care.

Irritable bowel syndrome (IBS) is a disorder of gut–brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.

Background: Aloe barbadensis Mill. (Aloe) extract was found to be well-tolerated, safe and showed beneficial effects in subsets of irritable bowel syndrome (IBS) patients in two randomized, double-blind, controlled studies. However, the individual studies were underpowered to perform subgroup analyses. We therefore determined the effect of Aloe extract in IBS subgroups in a post hoc analysis combining the results from the two studies. Methods: Data from the two controlled studies comparing Aloe and control treatment taken orally for 4 weeks, were pooled. Both studies included IBS patients fulfilling the ROME III criteria and IBS Symptom Severity Score (IBS-SSS) was assessed. We analysed the effect of Aloe extract on IBS symptom severity and the proportion of responders (IBS-SSS reduction ⩾ 50) in IBS subgroups. Results: In total, 213 IBS patients were included in the post hoc subgroup analyses. A reduction in overall symptom severity, primarily driven by effect on pain severity and frequency, comparing baseline versus end of treatment, was recorded in IBS patients with diarrhoea (IBS-D) receiving Aloe ( n = 38, p

Abstract Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map™ Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1–5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (≤ 50 mg/kg, n = 57) and increased (≥ 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI ≥ 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS. Trial registration ClinicalTrials.gov, NCT00858819. Registered March 9, 2009.

BackgroundIrritable bowel syndrome (IBS) is a multi-faceted gastrointestinal disorder where food intake often triggers symptoms. Metabolomics may provide mechanistical insights to why responses to dietary modifications are diverse.ObjectiveThis study aimed to identify metabolite patterns related to dietary intake in patients with IBS, and to identify metabolites driving the separation between responders and non-responders to treatment.MethodsParticipants were randomized to a low fermentable oligo-, di-, monosaccharide and polyol (FODMAP) diet (LFD) or traditional IBS diet (TID) for four weeks. Fasting serum and urine samples pre- and post-intervention were analyzed using 1H nuclear magnetic resonance (NMR) metabolomics. Response to treatment was defined as a reduction in IBS severity scoring system (IBS-SSS) ≥50.ResultsTwenty-five individuals in the LFD (13 responders) and 28 in the TID (14 responders) were included in these post hoc analyses. In endpoint samples, significant decreases in polyols and glucose were seen in the LFD. Post-intervention samples revealed that LFD responders had significantly increased levels of 2-hydroxybuturate and decreased levels of glucose and pantothenic acid compared to non-responders. For the TID, only weak multivariate models were identified and a larger diversity in metabolite response compared to the LFD were noted.ConclusionsIn this study, metabolite patterns between individuals who responded well to an LFD compared to non-responders could be distinguished. This provides new hypotheses for mechanistic actions related to response to dietary modifications, but the results need to be validated in larger cohorts.Clinical trial registrationThis trial was registered at www.clinicaltrials.gov, registry number NCT02107625.

Somatization, defined as the presence of multiple somatic symptoms, frequently occurs in irritable bowel syndrome (IBS) and may constitute the clinical manifestation of a neurobiological sensitization process. Brain imaging data was acquired with T1 weighted 3 tesla MRI, and gray matter morphometry were analyzed using FreeSurfer. We investigated differences in networks of structural covariance, based on graph analysis, between regional gray matter volumes in IBS-related brain regions between IBS patients with high and low somatization levels, and compared them to healthy controls (HCs). When comparing IBS low somatization (N = 31), IBS high somatization (N = 35), and HCs (N = 31), we found: (1) higher centrality and neighbourhood connectivity of prefrontal cortex subregions in IBS high somatization compared to healthy controls; (2) higher centrality of left cerebellum in IBS low somatization compared to both IBS high somatization and healthy controls; (3) higher centrality of the anterior insula in healthy controls compared to both IBS groups, and in IBS low compared to IBS high somatization. The altered structural covariance of prefrontal cortex and anterior insula in IBS high somatization implicates that prefrontal processes may be more important than insular in the neurobiological sensitization process associated with IBS high somatization.

Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-mapTM dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.

ObjectivesAim of this study was to assess the effect of a fermented milk product containing Bifidobacterium lactis CNCM I-2494 (FMP) on gastrointestinal (GI) symptoms and exhaled H2 and CH4 during a nutrient and lactulose challenge in patients with irritable bowel syndrome (IBS).MethodsWe included 125 patients with IBS (Rome III). Fasted subjects were served a 400ml liquid test meal containing 25g lactulose. The intensity of eight GI symptoms and the amount of exhaled H2 and CH4 were assessed before and during 4h after meal intake. The challenge was repeated after 14 days consumption of FMP or a control product in a double-blind, randomized, parallel design. The metabolic potential of fecal microbiota was profiled using 16S MiSeq analysis of samples obtained before and after the intervention.Results106 patients with IBS were randomized. No difference between FMP or control groups was found on GI symptoms or breath H2 and CH4 in the whole cohort. A post-hoc analysis in patients stratified according to their fasting H2 levels showed that in high H2 producers (fasting H2 level≥10ppm, n = 35), FMP consumption reduced fasting H2 levels (p = 0.003) and H2 production during the challenge (p = 0.002) and tended to decrease GI discomfort (p = 0.05) vs. control product. The Prevotella/Bacteroides metabolic potential at baseline was higher in high H2 producers (pConclusionsThe response to a fermented milk product containing Bifidobacterium lactis CNCM I-2494 (FMP) in patients with IBS seems to be associated with the metabolic potential of the gut microbiota.Trial registrationClinicalTrial.gov NCT01252550. These results were presented as congress posters at Digestive Disease Week 2016 in San Diego, USA and United European Gastroenterology Week 2016 in Vienna, Austria.

Functional gastrointestinal disorders (FGID), including irritable bowel syndrome, functional dyspepsia and functional abdominal pain, are common in adolescents and are associated with substantially decreased quality of life. Cognitive behavior therapy for children and adolescents with FGID is one of few treatments that have shown effect, but treatment access is limited. In adults with irritable bowel syndrome, exposure-based internet-delivered CBT (ICBT) leads to reduced symptoms and increased quality of life, but studies in children are lacking. This open pilot aimed to evaluate feasibility and the potential efficacy of an exposure-based ICBT-program for adolescents with pain-predominant FGID. Twenty-nine adolescents (age 13–17), with FGID were included. The ICBT-program lasted for 8 weeks with weekly online therapist support. The protocol for adolescents included exposure to abdominal symptoms, while the protocol for parents aimed at increasing parents' attention to adolescent healthy behaviors. Assessment points were baseline, post-treatment and 6-month follow-up. The primary outcome was the Gastrointestinal Symptoms Rating Scale-IBS (GSRS-IBS). Effect sizes were calculated using Cohen's d in an intent to treat analysis. GSRS-IBS improved significantly from baseline to post-treatment (mean difference 6.48; 95% CI [2.37–10.58]) and to follow-up (mean difference 7.82; 95% CI [3.43–12.21]), corresponding to moderate effect sizes (within-group Cohen's d = 0.50; 95% CI [0.16–0.84] and d = 0.63; 95% CI [0.24–1.02], respectively). Treatment adherence was high with 22 of 29 (76%) adolescents completing the entire treatment period. High adherence indicates acceptability of format and content, while symptomatic improvement suggests potential efficacy for this ICBT intervention in adolescents with FGID.

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder characterised by chronic and recurrent abdominal pain and altered bowel habit. Numerous pharmacological and non pharmacological treatment options have proven to have some benefit in the condition, and a multidisciplinary approach should ensure that treatment is tailored to the individual. Recently, an enhanced understanding of the pathophysiological processes underlying the condition has led to the development of new therapies, including prokinetic agents targeting serotonin (5-HT) pathways, and pro-secretory agents. Many are still at an early stage of clinical development, however, some have demonstrated improved outcomes in clinical trials and have gained regulatory approval. Lubiprostone, a calcium channel activator and linaclotide, a novel secretagogue that activates the guanylate cyclase C receptor, have demonstrated improvement of abdominal pain as well as improved bowel function in patients with IBS with constipation (IBS-C) in a series of randomised, placebo-controlled studies.

Functional gastrointestinal disorders are very common in the Western world, but unfortunately the underlying mechanisms behind these disorders are incompletely understood. Treatment options are limited and the economic consequences for society are profound. Recent data suggest an involvement of bacteria in the pathogenesis of functional gastrointestinal disorders. Probiotics are promising new treatment alternatives, which will be reviewed in this supplement.