Psychological adjustment and autonomic disturbances in inflammatory bowel diseases and irritable bowel syndrome.: Psychological and autonomic dysfunctions in IBD and IBS

International audiencePsychological factors and the autonomic nervous system (ANS) are implicated in the pathogenesis of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). This study aimed to assess, firstly the way IBS and IBD patients cope with their pathology according to their affective adjustment and secondly the possible links between these affective adjustments and ANS reactivity. Patients with Crohn's disease (CD; n=26), ulcerative colitis (UC; n=22), or IBS (n=27) were recruited and compared to 21 healthy subjects based on psychological variables (trait- and state anxiety, depressive symptomatology, negative mood, perceived stress, coping, health locus of control) and sympatho-vagal balance through heart-rate variability monitored at rest. A principal component analysis, performed on all affective variables, isolated a leading factor labelled as "affective adjustment". In each disease, patients were distributed into positive and negative affective adjustment. In all the diseases, a positive affect was associated with problem-focused coping, and a negative affect with emotion-focused coping and external health locus of control. Results show that the sympatho-vagal balance varied according to the disease. In CD presenting positive affectivity, an adapted high sympathetic activity was observed. In UC, a parasympathetic blunt was observed in the presence of negative affectivity and an equilibrated sympatho-vagal balance in the presence of positive affectivity. In contrast, in IBS, an important dysautonomia (with high sympathetic and low parasympathetic tone) was constantly observed whatever the affective adjustment. In conclusion, this study suggests that the equilibrium of the ANS is differentially adapted according to the disease. This equilibrium is conjugated with positive affective and cognitive adjustment in IBD (CD and UC) but not in IBS

Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs

peer-reviewedBackground: Carotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity. Methods: Adult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour−1) for 8 h.day−1 for 12 consecutive days. Findings: CIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls. Interpretation: Increased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing

Safety and efficacy of granulocyte/monocyte apheresis in steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics (ART trial): 12-week interim results

International audienceBACKGROUND AND AIMS: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup.METHODS: This single arm, open-label, multicentre trial (ART) was conducted at 18 centres across the UK, France and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate (clinical activity index ≤4) at Week 12.RESULTS: Eighty-six patients were enrolled. At Week 12, 33/84 (39.3%) of patients in the intention-to-treat population achieved clinical remission, with 47/84 (56.0%) achieving a clinical response (clinical activity index reduction of ≥3). Clinical remission was achieved in 30.0% of patients with prior immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life (Short Health Scale) significantly improved at Week 12 (p\textless0.0001). The majority of adverse events were of mild/moderate intensity.CONCLUSIONS: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgrou

The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update

Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion

Anti-inflammatory properties of the vagus nerve: therapeutic implications in gastroenterology

Le nerf vague assure la liaison entre le système nerveux central et le tube digestif. C’est un nerf mixte comprenant 80 % de fibres afférentes et 20 % de fibres efférentes. Il a des propriétés anti-inflammatoires à la fois via ses fibres afférentes capables d’activer l’axe corticotrope en réponse à un stress immunitaire et, de découverte plus récente, via ses fibres efférentes. En effet, la libération d’acétylcholine à l’extrémité de ses fibres efférentes est capable d’inhiber la libération de TNF par les macrophages. Cette propriété anti-TNF du nerf vague peut être utilisée dans le traitement des maladies inflammatoires chroniques de l’intestin mais également dans la polyarthrite rhumatoïde. La neurostimulation vagale peut avoir un intérêt dans cette approche thérapeutique non médicamenteuse en alternative aux anti-TNF conventionnels ou en alternative aux thérapies médicamenteuses.The vagus nerve is the link between the central nervous system and the digestive tract. It is a mixed nerve composed of 80% and 20% of afferent and efferent fibers respectively. The vagus nerve has anti-inflammatory properties both through its afferents, through the hypothalamic-pituitary adrenal axis, and more recently described, through its efferents. Indeed, the release of acetylcholine at the distal end of the vagus nerve is able to inhibit the release of TNF by macrophages. This anti-TNF effect could be used in the treatment of inflammatory bowel diseases but also rheumatoid arthritis. Vagus nerve stimulation may be of interest as a non-drug therapy in alternative to conventional anti-TNF or to drug therapies

Coastal Landscape and Public Use. A Landscape Architecture Proposal for the Los Limites Beach, Chubut, Argentina

Along the Argentinian Patagonia Coast private urbanization develops over public beach areas. This study presents the case of an area called Los Limites Beach situated along the Patagonian coast. After an analysis, survey and diagnosis of natural and social features, a landscape project was developed having the objective to protect Patagonian coastal landscape identity, preserving its natural components and encouraging its public use

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCG

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally

Validation of a Piles Dynamic Analysis Computer Code Through In Situ Tests

In order to qualify the CLAPIFOU code, which computes the dynamic response of a pile foundation subjected to earthquake or harmonic forces, a test campaign was carried out on piles, to full scale, on pile groups of 2 x 1 piles and 2 x 3 piles on the Plancoet site. The purpose of the study is to compare the results of the experiments and the digital simulations with the computer code. The comparison is good but confirms the need for a good knowledge of the soil\u27s characteristics

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS)

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally