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This study evaluated the association between dietary patterns, gas-related symptoms (GRS) and their impact on quality of life (QoL) in a representative sample (n 936) of the French adult population. During the 2018–2019 ‘Comportements et Consommations Alimentaires en France’ survey (Behaviors and Food Consumption in France), online evaluation of GRS in adult participants was performed using the validated Intestinal Gas Questionnaire (IGQ), which captures the perception of GRS and their impact on QoL via six symptom dimensions scores (range 0–100; 100 = worse) and a global score (mean of the sum of the six symptom dimensions scores). Socio-demographics, lifestyle parameters and dietary habits (7-d e-food diary) were also collected online. Quality of diet was determined using the Nutrient-Rich Food 9.3 (NRF9.3) score (range 0–900; 900 = best). Univariate and multivariate linear regression models were applied to identify factors associated with IGQ global score. K-means was used to identify clusters of subjects based on their dietary records. Data from 936 adults who completed both the IGQ and the food diary showed a mean IGQ global score of 11·9 (sd 11·2). Younger age and female sex were associated with a higher IGQ global score. Only 7 % of subjects reported no symptom at all and nearly 30 % of study participants reported a high impact of GRS on their QoL. Two dietary clusters were identified: cluster 1, characterised by a higher consumption of fruits and vegetables, lower sugars intake and higher NRF9.3 score and cluster 2, characterised by higher intake of sugars, lower intake in dietary fibres and lower NRF9.3 score. The IGQ global score was lower in cluster 1 and higher in cluster 2 v. the total sample average (P < 0·001). The prevalence of GRS in the French adult population is high and is associated with impaired QoL and dietary patterns. A change in food habits towards healthier patterns could help reducing the burden of GRS.

Background Gastrointestinal (GI) discomfort is prevalent and known to be associated with impaired quality of life. Real-world information on factors of GI discomfort and solutions used by people is, however, limited. Social media, including online forums, have been considered a new source of information to examine the health of populations in real-life settings. Objective The aims of this retrospective infodemiology study are to identify discussion topics, characterize users, and identify perceived determinants of GI discomfort in web-based messages posted by users of French social media. Methods Messages related to GI discomfort posted between January 2003 and August 2018 were extracted from 14 French-speaking general and specialized publicly available online forums. Extracted messages were cleaned and deidentified. Relevant medical concepts were determined on the basis of the Medical Dictionary for Regulatory Activities and vernacular terms. The identification of discussion topics was carried out by using a correlated topic model on the basis of the latent Dirichlet allocation. A nonsupervised clustering algorithm was applied to cluster forum users according to the reported symptoms of GI discomfort, discussion topics, and activity on online forums. Users’ age and gender were determined by linear regression and application of a support vector machine, respectively, to characterize the identified clusters according to demographic parameters. Perceived factors of GI discomfort were classified by a combined method on the basis of syntactic analysis to identify messages with causality terms and a second topic modeling in a relevant segment of phrases. Results A total of 198,866 messages associated with GI discomfort were included in the analysis corpus after extraction and cleaning. These messages were posted by 36,989 separate web users, most of them being women younger than 40 years. Everyday life, diet, digestion, abdominal pain, impact on the quality of life, and tips to manage stress were among the most discussed topics. Segmentation of users identified 5 clusters corresponding to chronic and acute GI concerns. Diet topic was associated with each cluster, and stress was strongly associated with abdominal pain. Psychological factors, food, and allergens were perceived as the main causes of GI discomfort by web users. Conclusions GI discomfort is actively discussed by web users. This study reveals a complex relationship between food, stress, and GI discomfort. Our approach has shown that identifying web-based discussion topics associated with GI discomfort and its perceived factors is feasible and can serve as a complementary source of real-world evidence for caregivers.

While several studies have documented associations between dietary habits and microbiota composition and function in healthy subjects, no study explored these associations in patients with irritable bowel syndrome (IBS), and especially in relation to symptoms. Here, we used a novel approach that combined data from 4-day food diary, integrated into a food tree, together with gut microbiota (shotgun metagenomic) for IBS patients (N=149) and healthy subjects (N=52). Paired microbiota and food-based trees allowed to detect new association 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. IBS patients with severe symptoms had a diet enriched in food items of poorer quality, a high abundance of gut microbial enzymes involved in hydrogen metabolism in correlation with animal carbohydrate (mucin/meat-derived) metabolism. Our study provides unprecedented resolution of diet-microbiota-symptom interactions and ultimately paves the way for personalized nutritional recommendations.

Background: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets. Methods: In an open design, a 3-day high-residue diet was administered to healthy subjects (n = 74 included, n = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. Main outcomes: digestive sensations, number of daytime anal gas evacuations, and gas volume evacuated during 4 h after a probe meal. Results: As compared to the habitual diet, the high-residue diet induced gas-related symptoms (flatulence score 4.9 vs. 1.2; p ≤ 0.0001), increased the daily number of anal gas evacuations (20.7 vs. 8.7; p < 0.0001), and impaired digestive well-being (1.0 vs. 3.4; p < 0.05). FMP consumption reduced flatulence sensation (by −1.7 [−1.9; −1.6]; p < 0.0001), reduced the number of daily evacuations (by −5.8 [−6.5; −5.1]; p < 0.0001), and improved digestive well-being (by +0.6 [+0.4; +0.7]; p < 0.05). FMP consumption did not affect the gas volume evacuated after a probe meal. Conclusion: In healthy subjects, consumption of a FMP containing B. lactis CNCM I-2494 and lactic acid bacteria improves the tolerance of a flatulogenic diet by subjective and objective criteria (sensations and number of anal gas evacuations, respectively).

BACKGROUND Gastrointestinal (GI) discomfort is prevalent and known to be associated with impaired quality of life. Real-world information on factors of GI discomfort and solutions used by people is, however, limited. Social media, including online forums, have been considered a new source of information to examine the health of populations in real-life settings. OBJECTIVE The aims of this retrospective infodemiology study are to identify discussion topics, characterize users, and identify perceived determinants of GI discomfort in web-based messages posted by users of French social media. METHODS Messages related to GI discomfort posted between January 2003 and August 2018 were extracted from 14 French-speaking general and specialized publicly available online forums. Extracted messages were cleaned and deidentified. Relevant medical concepts were determined on the basis of the Medical Dictionary for Regulatory Activities and vernacular terms. The identification of discussion topics was carried out by using a correlated topic model on the basis of the latent Dirichlet allocation. A nonsupervised clustering algorithm was applied to cluster forum users according to the reported symptoms of GI discomfort, discussion topics, and activity on online forums. Users’ age and gender were determined by linear regression and application of a support vector machine, respectively, to characterize the identified clusters according to demographic parameters. Perceived factors of GI discomfort were classified by a combined method on the basis of syntactic analysis to identify messages with causality terms and a second topic modeling in a relevant segment of phrases. RESULTS A total of 198,866 messages associated with GI discomfort were included in the analysis corpus after extraction and cleaning. These messages were posted by 36,989 separate web users, most of them being women younger than 40 years. Everyday life, diet, digestion, abdominal pain, impact on the quality of life, and tips to manage stress were among the most discussed topics. Segmentation of users identified 5 clusters corresponding to chronic and acute GI concerns. Diet topic was associated with each cluster, and stress was strongly associated with abdominal pain. Psychological factors, food, and allergens were perceived as the main causes of GI discomfort by web users. CONCLUSIONS GI discomfort is actively discussed by web users. This study reveals a complex relationship between food, stress, and GI discomfort. Our approach has shown that identifying web-based discussion topics associated with GI discomfort and its perceived factors is feasible and can serve as a complementary source of real-world evidence for caregivers.

ObjectiveBrain-gut-microbiota interactions may play an important role in human health and behavior. Although rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive, and social behaviors, there is little translational human evidence to date. In this study, we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles.MethodsForty women supplied fecal samples for 16S rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota clusters using white and gray matter metrics.ResultsTwo bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n = 33) and one with greater Prevotella abundance (n = 7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2%, respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus.ConclusionsThese results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain, and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior.

Background This study aimed to determine whether patients with IBS displayed altered mucosal mast cell (MC) numbers and proportions of MCs co-localizing with nerves compared with healthy subjects (HS) and whether these MC characteristics correlated with IBS symptoms, elements of the epithelial barrier, or visceral sensitivity. Methods Mucosal MC characteristics were determined using immunoassay. IBS symptoms, gene expression of elements of the epithelial barrier, fecal serine protease activity, and visceral sensitivity were assessed. Key results The MC numbers per mm2 were 2.0 (0.0-6.0) in patients with IBS (n = 43) and 3.5 (1.1-9.1) in HS (n = 20, P = .26). Of these, MCs were 0.0 (0.0-20) % vs 3.1 (0.0-18) % (P = .76) in IBS and HS, respectively, in co-localization with nerve fibers. MC characteristics were equivalent in the different IBS subtypes. Hierarchical cluster analysis identified two distinct groups among patients with IBS: MC high (higher MC numbers and proportions of MCs co-localizing with nerves) and MC low (lower MC numbers and proportions of MCs co-localizing with nerves). The MC high and MC low groups could not be discriminated with regard to IBS symptoms, parameters of visceral sensitivity, gene expression of elements of the epithelial barrier, and fecal protease activity. Conclusion and inferences There was no evidence of increased infiltration or altered localization of MCs in the colonic mucosa of patients with IBS. These MC characteristics were not linked to global IBS symptoms or mucosal expression of elements of the epithelial barrier. These findings indicate that quantity and location of mucosal MCs are factors not involved in the pathophysiology of IBS.

Background and aims Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. Methods We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. Results We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. Conclusions In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS—these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system. Electronic supplementary material The online version of this article (10.1186/s40168-019-0656-z) contains supplementary material, which is available to authorized users.

Background A diet low in fermentable carbohydrates, fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) is a promising treatment option for patients with irritable bowel syndrome (IBS). In order to correctly estimate and study the intake of FODMAPs, information about within- and between-subject variations in intakes is needed, but is currently lacking. Objectives The aim was to characterize the variation in FODMAP intake among patients with IBS and to calculate how many days of observations are required to capture absolute intakes as well as to rank individuals. Methods Food intake was recorded during 4 consecutive days, and intakes of energy and FODMAPs were calculated. The coefficient of variation within subjects (CVw), coefficient of variation between subjects (CVb), number of days required to estimate an individual's intake, and number of observations required to correctly rank individuals into quartiles of consumption were calculated. Results Diet records were provided from 151 women and 46 men with IBS. The reported mean energy intake was 2039 ± 502 kcal among women and 2385 ± 573 kcal among men, and the median FODMAP intakes were 18.7 g (range 3.7-73.4) and 22.8 g (range 3.6-165.7), respectively. The ratio of CVw/CVb for total FODMAP intake was 0.83 for women and 0.67 for men, and below 1 for all FODMAPs. To capture intake of FODMAPs at the individual level, 19 d of observations are required. Ranking individuals within a group would require 2-6 d of observations. Conclusion There is more variation between subjects than within subjects regarding FODMAP intake. To correctly estimate an individual's absolute intake of FODMAPs, the number of days of diet records required exceeds what is reasonable for a participant to accomplish. However, ranking individuals into quartiles of FODMAP consumption can be achieved using a 4-d food record. This trial was registered at www.clinicaltrials.gov as NCT02107625 and NCT01252550.

Background. Minor digestive symptoms are common and dietary approaches such as probiotic administration or fibre and fermentable carbohydrate intake adjustments are often recommended. A Fermented Milk Product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria has been shown to improve digestive symptoms after 4 weeks of consumption, but the speed of onset of this effect and its dependence on fibre intake or physical activity is unknown. To answer these questions, data from two previously published trials on FMP for minor digestive symptoms were combined. Methods. In total, 538 participants provided weekly assessments of bloating, abdominal pain/discomfort, flatulence, borborygmi/rumbling stomach from which a composite score was calculated. At baseline in one study (n = 336), dietary fibre consumption was recorded and physical activity classified as high, moderate or low. The speed of the FMP’s effect was assessed by a repeated measure analysis of variance measuring the change from baseline for the composite score of digestive symptoms. Results. FMP consumption resulted in a significant decrease in the composite score of symptoms after only 2 weeks in both studies and the pooled data at week 1 (−0.35 [−0.69, 0.00]; p = 0.05), week 2 (−0.66 [−1.04, −0.27]; p < 0.001), week 3 (−0.49 [−0.89, −0.10]; p = 0.01) and week 4 (−0.46 [−0.88, −0.04]; p = 0.03). The interactions fibre intake-by-product group, physical activity-by-product group and time-by-product group were not statistically significant. Conclusion. FMP consumption leads to a rapid improvement in symptoms which is likely to encourage adherence to this dietary intervention. This effect is independent of dietary fibre and physical activity.

Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms.Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed.Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified.Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.

Background: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets. Methods: In an open design, a 3-day high-residue diet was administered to healthy subjects (n = 74 included, n = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. Main outcomes: digestive sensations, number of daytime anal gas evacuations, and gas volume evacuated during 4 h after a probe meal. Results: As compared to the habitual diet, the high-residue diet induced gas-related symptoms (flatulence score 4.9 vs. 1.2, p &le, 0.0001), increased the daily number of anal gas evacuations (20.7 vs. 8.7, p &lt, 0.0001), and impaired digestive well-being (1.0 vs. 3.4, 0.05). FMP consumption reduced flatulence sensation (by &minus, 1.7 [&minus, 1.9, &minus, 1.6], 0.0001), reduced the number of daily evacuations (by &minus, 5.8 [&minus, 6.5, 5.1], 0.0001), and improved digestive well-being (by +0.6 [+0.4, +0.7], 0.05). FMP consumption did not affect the gas volume evacuated after a probe meal. Conclusion: In healthy subjects, consumption of a FMP containing B. lactis CNCM I-2494 and lactic acid bacteria improves the tolerance of a flatulogenic diet by subjective and objective criteria (sensations and number of anal gas evacuations, respectively).

International audience; Altered fecal levels of chromogranins (Cg) and secretogranins (Sg) are demonstrated in irritable bowel syndrome (IBS), but their role in IBS pathophysiology remains unknown. This study aimed to determine if granins are associated with bacterial composition, immune activation and IBS symptoms. Protein levels of fecal granins (CgA, CgB, SgII and SgIII) were analysed with immunoassays. Mucosal mRNA expression of granins, TPH1 and immune markers were evaluated with RT-qPCR. 16S rRNA gene sequencing was performed on fecal and mucosal bacteria. The intestinal granin profile, based on fecal protein levels and mucosal mRNA expression, could not discriminate between IBS patients (n = 88) and healthy subjects (HS, n = 33). IBS patients dominated by high fecal or mucosal granin levels, respectively, did not differ in symptom or immune profiles. Fecal-dominated and mucosal-dominated granin clusters of IBS patients and HS, demonstrated separate fecal and mucosal bacterial profiles and high fecal abundance of granins were associated with a less diverse bacterial composition and the Bacteroides enterotype. The intestinal granin profiles of IBS patients and HS are linked to the intestinal bacterial composition, diversity and enterotypes. These findings suggest that granins may be one of several host-produced factors regulating the microbiota composition of the intestine.

BACKGROUND & AIMS: We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms. METHODS: We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at secondary or tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H2 and CH4, oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numeric ecology analyses and a machine learning procedure were used to analyze the data. RESULTS: Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with vs without IBS. A computational statistical technique-like machine learning procedure allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications. CONCLUSIONS: In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms. TRIAL REGISTRATION NUMBER: NCT01252550. CC BY-NC-ND 4.0

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.

Background. Minor digestive symptoms are common and dietary approaches such as probiotic administration or fibre and fermentable carbohydrate intake adjustments are often recommended. A Fermented Milk Product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria has been shown to improve digestive symptoms after 4 weeks of consumption, but the speed of onset of this effect and its dependence on fibre intake or physical activity is unknown. To answer these questions, data from two previously published trials on FMP for minor digestive symptoms were combined. Methods. In total, 538 participants provided weekly assessments of bloating, abdominal pain/discomfort, flatulence, borborygmi/rumbling stomach from which a composite score was calculated. At baseline in one study (n = 336), dietary fibre consumption was recorded and physical activity classified as high, moderate or low. The speed of the FMP&rsquo, s effect was assessed by a repeated measure analysis of variance measuring the change from baseline for the composite score of digestive symptoms. Results. FMP consumption resulted in a significant decrease in the composite score of symptoms after only 2 weeks in both studies and the pooled data at week 1 (&minus, 0.35 [&minus, 0.69, 0.00], p = 0.05), week 2 (&minus, 0.66 [&minus, 1.04, &minus, 0.27], p &lt, 0.001), week 3 (&minus, 0.49 [&minus, 0.89, &minus, 0.10], p = 0.01) and week 4 (&minus, 0.46 [&minus, 0.88, &minus, 0.04], p = 0.03). The interactions fibre intake-by-product group, physical activity-by-product group and time-by-product group were not statistically significant. Conclusion. FMP consumption leads to a rapid improvement in symptoms which is likely to encourage adherence to this dietary intervention. This effect is independent of dietary fibre and physical activity.

Patients with irritable bowel syndrome (IBS) have an increased response of postprandial symptoms to a combined lactulose nutrient challenge test, compared with healthy volunteers. We investigated the associations among comorbid functional dyspepsia (FD), severity of psychologic symptoms, and breath test results in response to this test.We performed a prospective study of 205 patients with IBS (Rome III criteria), 94 of whom also had FD (IBS-FD), and 83 healthy volunteers in Sweden from 2008 through 2015. All participants completed a breath hydrogen test after a 400-mL liquid meal with 25 g lactulose. Gastrointestinal (GI) symptom severity was assessed using a graded scale and digestive comfort was recorded before the meal and every 15 minutes until 240 minutes after the meal. GI symptom scores over time were compared between groups using linear mixed models with anxiety, depression, and somatization as covariates.Average levels of all GI symptoms varied over time among all groups (P.0001). Patients with IBS-FD had higher levels of bloating (P = .004), abdominal pain (P = .005), and lower levels of digestive comfort (P.01) than patients with only IBS. We observed a difference in increase in abdominal pain from baseline between IBS-FD and IBS groups (P = .013). Anxiety levels were associated with levels of all symptoms (all P.025) except abdominal pain, which was associated with somatization severity (P.0001). Furthermore, anxiety levels associated with level of exhaled hydrogen (P = .0042).In a prospective study of patients with IBS, we found those with FD to have increased GI symptoms before and after a liquid meal with lactulose. Anxiety and somatization have an independent additional effect. The presence of comorbid FD and levels of psychologic symptoms affect reports of food-related symptoms in patients with IBS. ClinicalTrial.gov no: NCT01252550.

We read with interest the letter commenting on our recent article.1 The first question raised by Philpott et al2 is whether lactulose alone, without the combined liquid meal used in our study, would be as effective in producing the abdominal distension and symptoms characteristic of irritable bowel syndrome (IBS). The initial aim of our combined nutrient and lactulose challenge was to experimentally reproduce the digestive symptoms elicited by meals in IBS patients in a standardized way, and to add the effects of fermentation of poorly absorbed carbohydrates.

International audience; BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) can be assigned to groups with different gastrointestinal (GI) symptoms based on results from a combined nutrient and lactulose challenge. We aimed to identify factors that predict outcomes to this challenge and to determine whether this can be used in noninvasive assessment of visceral sensitivity in patients with IBS. METHODS: We performed a prospective study of 100 patients with IBS diagnosed according to Rome III criteria (all subtypes) and seen at a secondary or tertiary care center. After an overnight fast, subjects were given a liquid breakfast (400 mL; Nutridrink) that contained 25 g lactulose. Before the challenge, we assessed visceral sensitivity (via rectal barostat), oro-anal transit time, and fecal microbiota composition (via 16S ribosomal RNA pyrosequencing); we determined IBS severity using questionnaires. The intensity of 8 GI symptoms, the level of digestive comfort, and the amount of exhaled H-2 and CH4 in breath were measured before and during a 4-hour period after the liquid breakfast. RESULTS: Based on the intensity of 8 GI symptoms and level of digestive comfort during the challenge, patients were assigned to groups with high-intensity GI symptoms (HGS; n = 39) or low-intensity GI symptoms (LGS; n [ 61); patients with HGS had more severe IBS (P

Enteroendocrine cells in the intestine sense the luminal contents and have been shown to respond to not only fatty acids, proteins, and monosaccharides but also artificial sweeteners and bitter compounds. Secretion of hormones such as CCK and GLP-1 from these cells is often associated with a rise in intracellular calcium concentration [Ca²+](i). The human NCI-H716 enteroendocrine cell line has been described as a proper model to study GLP-1 secretion in response to amino acids and protein hydrolysates. Here, we describe that NCI-H716 cells specifically respond to selective tetrapeptides such as tetra-glycine, tetra-alanine and Gly-Trp-Gly-Gly with a dose-dependent [Ca²+](i) response and a GLP-1 secretion, whereas selected free amino acids, dipeptides, tripeptides and pentapeptides failed to elicit such a response. Hormone secretion was not associated with changes in cAMP levels in the cells. The calcium-dependence of hormone secretion appears to involve store-operated calcium channels (SOCCs), since the SOCC blocker 2-APB abolished both the [Ca²+](i) response and GLP-1 release upon tetra-glycine stimulation. The nature of the sensor currently remains elusive, and no obvious common structural pattern in tetrapeptides eliciting GLP-1 secretion was identified. This tetrapeptide sensing in NCI-H716 cells may be underlying the effective stimulation of hormone secretion shown for various protein hydrolysates, and could involve a novel G-protein-coupled receptor (GPCR).

International audience; Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.

Steroid glycosides extracted from the succulent plant Hoodia gordonii are suggested to have appetite-suppressant effects both in animals and humans. Yet, the mechanisms underlying the putative satiety action of Hoodia steroid glycosides are not fully understood. We found that H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine (EC) cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve which afferents terminate in the gut wall. Recent data show that G protein-coupled receptors signaling bitter taste (T2Rs) are expressed in both rodent and human gastrointestinal tract. It was further demonstrated that bitter sensing is functional in mouse STC-1 EC cells and leads to CCK secretion via increased intracellular Ca2+ concentrations. Based on the bitter taste of H. gordonii purified extracts, we assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. Removing an essential structural feature from the steroid glycoside inhibited H.g.-12-induced Ca2+ increase in TAS2R14-expressing HEK cells and abolished H.g.-12-induced CCK secretion from human EC cells. Similarly, a nonspecific bitter receptor antagonist abolished H.g.-12-induced CCK secretion in HuTu-80 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control. Our data also provide additional evidence that bitter taste-sensing mechanisms are coupled to hormone release from EC cells in the intestine. Moreover, we identified a natural agonist of TAS2R7 and TAS2R14 for further studies on the role of bitter receptors in satiety control and food intake.

Background: Idiopathic bile acid malabsorption (BAM) causes chronic diarrhea and BA deficiency may cause constipation. BA supplementation and an ileal BA transporter inhibitor, elobixibat, accelerate colonic transit (CT). Rectal infusion of BA (e.g. chenodeoxycholate) induces colonic propulsive motility. Up to 50% of patients with IBS-D have accelerated CT; 20% of patients with IBS-C have delayed CT. The relationship between fecal BA excretion, CT, and bowel symptoms in IBS is unclear and may be relevant to selecting optimal therapy. Aim: To assess stool frequency (number) and consistency (form) in relation to CT and fecal BA excretion in healthy participants and patients with IBS-C and IBS-D. Methods: In a prospective study of 92 participants (31 healthy, 30 IBS-C and 31 IBS-D by Rome III criteria), we measured total and individual fecal BA and fecal fat (on 100g fat diet), overall CT by validated scintigraphy (geometric center, GC at 24 and 48h) and stool characteristics by a 14 day bowel pattern diary including Bristol stool form scale. Univariate associations between endpoints were assessed using Spearman correlation (rs). Relationships between stool characteristics, CT and fecal BA excretion were assessed using response surface multiple regression models (which included BMI as a covariate and linear, quadratic and cross product terms for the CT and BA measurements). Results: 1. There were significant univariate associations (table showing rs) between stool number and stool form and total fecal BA (including % LCA, % CDCA, and % CA), fecal fat, and GC24 and 48. 2. The response surface model for stool number (figure left panel) with total fecal BA and CT (GC24 ) explained 29% of the variation (r=0.54, p,0.001); similarly, the model for stool form (figure middle panel) with fecal BA and CT (GC24) explained 20% of the variation (r=0.45, p=0.021). Using total secretory BA (CA+DCA+CDCA), the response surface model for stool form (figure right panel) explained 23% of the variation (r=0.49, p=0.006). In these models, the relative contribution of CT was consistently greater than that for BA, with the coefficients corresponding to CT being statistically significant (p,0.05), while those for BA were borderline (e.g. p=0.073 for the coefficient for secretory BA and stool form, and p=0.227 for stool number). Conclusion: Relative to fecal BA, colonic transit is the greater determinant of stool number and stool form; increased total and secretory fecal BA enhance the effects of colon transit on stool characteristics, but are not independently significant factors. Funding:NIHDK92179

Background: Postprandial worsening of symptoms is common in patients with irritable bowel syndrome (IBS), and alterations in the gut microbiota may be involved in IBS symptom generation. Lactulose is a non-digestible carbohydrate fermented by gut bacteria, which might serve as a tool to study bacterial involvement in postprandial symptom generation. Aim: To evaluate the usefulness of a test meal containing lactulose in the assessment of gastrointestinal (GI) symptom generation in IBS. Methods: We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served each of the three test meals consisting in a 400ml liquid breakfast (Nutridrink®, 1.5 kcal/ml) containing lactulose (15g or 25g) or no additive (nutrient only) at least one week apart in a doubleblind randomized protocol. The severity of GI symptoms, anxiety and depression were evaluated by questionnaire before the test, and seven GI symptoms, the overall level of digestive comfort and the amount of exhaled H2/CH4 were assessed every 15min during 4hrs after meal intake. A 4h mean AUC for individual symptoms and a Principal Components Analysis (PCA) on all symptoms followed by cluster analysis were performed in IBS patients. Results: All three test meals were well tolerated by all subjects. IBS subjects showed significantly higher scores than controls on all symptoms for the three test meals. No correlation was found between amount of exhaled gas and severity of symptoms. PCA showed a strong negative correlation between overall digestive comfort and bloating, discomfort and distension, the most representative symptoms induced by the challenge. The 25g dose induced the highest scores in IBS for bloating, discomfort and distension (8.7±4.8, 10.0±5.3, 9.7±5.4) but did not differ significantly from the 15g dose (7.8±4.6, 8.3±5.3, 8.7±5.3). A 25g lactulose challenge allowed clustering of IBS subjects in two separated subgroups based on their symptom response. Patients in the High GI symptom group (n=16; 13.2±3.3, 14.4±3.2, 14.2±3.3) displayed higher levels of general anxiety (9.2±4.3 vs. 5.5±3.4; p