Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models

peer reviewedInflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn’s disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

La restriction de l’apport alimentaire préventive dans la prise en charge des maladies inflammatoires chroniques de l’intestin dans un modèle murin

Among the most common symptoms of inflammatory bowel disease (IBD, which includes ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea and weight loss. Not surprisingly, clinicians and patients alike wonder whether eating habits influence the onset or progression of IBD. The question of diet is one of the most frequently asked by patients and one of the most challenging for clinicians. Recent studies have revealed that dietary restriction is able to modulate the immune system and contribute to intervention in immune disorders. Here, we analyzed the therapeutic effect of customized intermittent dietary restriction (DR) on the dextran sulfate sodium (DSS)-induced chronic IBD model in mice. After defining the optimal percentage of restriction, four cycles of DR were administered before the onset of IBD symptoms in mice. Administration of DR significantly reduced the disease activity index score. DR reversed DSS-induced shortening of colon length, endoscopic score, fecal lipocalin, and improved intestinal permeability. The expression of an inflammation marker NLRP3 was also reduced by DR administration, while regulating monocarbon metabolite metabolism related to NLRP3 activation. In addition, application of DR altered local pro- and anti-inflammatory cytokine expression, including IL-17a, IL-1β, IL-6, and INFγ. Environmental factors, mucosal permeability, and defective immunoregulation result in excessive immunity to a subset of resident gut bacteria that mediate multiple inflammatory conditions. The establishment of DR down-regulates the pro-inflammatory power of the microbiota. The establishment of a DR in a chronic manner also has an impact on the composition of the microbiota, which is more important in the early stages. Cumulatively, the results indicate that dietary restriction may be an optional approach for the treatment of colitis, alone or in combination with immunosuppressive agents, or as a rescue treatment for patients who do not respond or become less responsive to medical treatments.Parmi les symptômes les plus courants des maladies inflammatoires de l'intestin (MICI, qui comprennent la colite ulcéreuse et la maladie de Crohn) figurent les douleurs abdominales, la diarrhée et la perte de poids. Il n'est donc pas surprenant que les cliniciens et les patients se demandent si les habitudes alimentaires influencent l'apparition ou l'évolution des MICI. La question de l'alimentation est l'une des plus fréquemment posées par les patients et l'une des plus difficiles à résoudre pour les cliniciens. Des études récentes ont révélé que la restriction alimentaire est capable de moduler le système immunitaire et de contribuer à l'intervention dans les troubles immunitaires. Nous avons analysé ici l'effet thérapeutique de la restriction alimentaire (DR) intermittente personnalisé sur le modèle de MICI chronique induite par le sulfate de dextran sodique (DSS) chez la souris. Après avoir défini le pourcentage de restriction optimal, quatre cycles de DR ont été administrés avant l'apparition des symptômes des MICI chez les souris. L'administration de DR a réduit de manière significative le score de l'indice d'activité de la maladie. La DR a inversé le raccourcissement de la longueur du côlon induit par le DSS, le score endoscopique, la lipocaline fécale et améliore la perméabilité intestinale. L'expression d'un marqueur d'inflammation NLRP3 a également été réduite par l'administration de DR, tout en régulant le métabolisme des métabolites des monocarbones lié à l’activation de NLRP3. En outre, l'application de la DR à modifié l’expression local de cytokine pro et anti-inflammatoire, notamment IL-17a, IL-1β, IL-6 et INFγ. Les facteurs environnementaux, la perméabilité de la muqueuse et une immunorégulation défectueuse entraînent une immunité excessive à un sous-ensemble de bactéries intestinales résidentes qui médient de multiples conditions inflammatoires. La mise en place de la DR permet de réguler à la baisse le pouvoir pro-inflammatoire du microbiote. La mise en place d’une DR de manière chronique à également un impact sur la composition du microbiote, impact plus important dans les temps précoce. Dans l'ensemble, les résultats indiquent que la restriction alimentaire peut être une approche optionnelle pour le traitement de la colite , seuls ou en association avec des agents immunosuppresseurs, ou comme traitement de secours pour les patients qui ne répondent pas ou deviennent moins sensibles aux traitements médicaux

Preventive diet restriction in the management of chronic inflammatory bowel disease in a mouse model

Parmi les symptômes les plus courants des maladies inflammatoires de l'intestin (MICI, qui comprennent la colite ulcéreuse et la maladie de Crohn) figurent les douleurs abdominales, la diarrhée et la perte de poids. Il n'est donc pas surprenant que les cliniciens et les patients se demandent si les habitudes alimentaires influencent l'apparition ou l'évolution des MICI. La question de l'alimentation est l'une des plus fréquemment posées par les patients et l'une des plus difficiles à résoudre pour les cliniciens. Des études récentes ont révélé que la restriction alimentaire est capable de moduler le système immunitaire et de contribuer à l'intervention dans les troubles immunitaires. Nous avons analysé ici l'effet thérapeutique de la restriction alimentaire (DR) intermittente personnalisé sur le modèle de MICI chronique induite par le sulfate de dextran sodique (DSS) chez la souris. Après avoir défini le pourcentage de restriction optimal, quatre cycles de DR ont été administrés avant l'apparition des symptômes des MICI chez les souris. L'administration de DR a réduit de manière significative le score de l'indice d'activité de la maladie. La DR a inversé le raccourcissement de la longueur du côlon induit par le DSS, le score endoscopique, la lipocaline fécale et améliore la perméabilité intestinale. L'expression d'un marqueur d'inflammation NLRP3 a également été réduite par l'administration de DR, tout en régulant le métabolisme des métabolites des monocarbones lié à l’activation de NLRP3. En outre, l'application de la DR à modifié l’expression local de cytokine pro et anti-inflammatoire, notamment IL-17a, IL-1β, IL-6 et INFγ. Les facteurs environnementaux, la perméabilité de la muqueuse et une immunorégulation défectueuse entraînent une immunité excessive à un sous-ensemble de bactéries intestinales résidentes qui médient de multiples conditions inflammatoires. La mise en place de la DR permet de réguler à la baisse le pouvoir pro-inflammatoire du microbiote. La mise en place d’une DR de manière chronique à également un impact sur la composition du microbiote, impact plus important dans les temps précoce. Dans l'ensemble, les résultats indiquent que la restriction alimentaire peut être une approche optionnelle pour le traitement de la colite , seuls ou en association avec des agents immunosuppresseurs, ou comme traitement de secours pour les patients qui ne répondent pas ou deviennent moins sensibles aux traitements médicaux.Among the most common symptoms of inflammatory bowel disease (IBD, which includes ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea and weight loss. Not surprisingly, clinicians and patients alike wonder whether eating habits influence the onset or progression of IBD. The question of diet is one of the most frequently asked by patients and one of the most challenging for clinicians. Recent studies have revealed that dietary restriction is able to modulate the immune system and contribute to intervention in immune disorders. Here, we analyzed the therapeutic effect of customized intermittent dietary restriction (DR) on the dextran sulfate sodium (DSS)-induced chronic IBD model in mice. After defining the optimal percentage of restriction, four cycles of DR were administered before the onset of IBD symptoms in mice. Administration of DR significantly reduced the disease activity index score. DR reversed DSS-induced shortening of colon length, endoscopic score, fecal lipocalin, and improved intestinal permeability. The expression of an inflammation marker NLRP3 was also reduced by DR administration, while regulating monocarbon metabolite metabolism related to NLRP3 activation. In addition, application of DR altered local pro- and anti-inflammatory cytokine expression, including IL-17a, IL-1β, IL-6, and INFγ. Environmental factors, mucosal permeability, and defective immunoregulation result in excessive immunity to a subset of resident gut bacteria that mediate multiple inflammatory conditions. The establishment of DR down-regulates the pro-inflammatory power of the microbiota. The establishment of a DR in a chronic manner also has an impact on the composition of the microbiota, which is more important in the early stages. Cumulatively, the results indicate that dietary restriction may be an optional approach for the treatment of colitis, alone or in combination with immunosuppressive agents, or as a rescue treatment for patients who do not respond or become less responsive to medical treatments

La restriction de l’apport alimentaire préventive dans la prise en charge des maladies inflammatoires chroniques de l’intestin dans un modèle murin

Among the most common symptoms of inflammatory bowel disease (IBD, which includes ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea and weight loss. Not surprisingly, clinicians and patients alike wonder whether eating habits influence the onset or progression of IBD. The question of diet is one of the most frequently asked by patients and one of the most challenging for clinicians. Recent studies have revealed that dietary restriction is able to modulate the immune system and contribute to intervention in immune disorders. Here, we analyzed the therapeutic effect of customized intermittent dietary restriction (DR) on the dextran sulfate sodium (DSS)-induced chronic IBD model in mice. After defining the optimal percentage of restriction, four cycles of DR were administered before the onset of IBD symptoms in mice. Administration of DR significantly reduced the disease activity index score. DR reversed DSS-induced shortening of colon length, endoscopic score, fecal lipocalin, and improved intestinal permeability. The expression of an inflammation marker NLRP3 was also reduced by DR administration, while regulating monocarbon metabolite metabolism related to NLRP3 activation. In addition, application of DR altered local pro- and anti-inflammatory cytokine expression, including IL-17a, IL-1β, IL-6, and INFγ. Environmental factors, mucosal permeability, and defective immunoregulation result in excessive immunity to a subset of resident gut bacteria that mediate multiple inflammatory conditions. The establishment of DR down-regulates the pro-inflammatory power of the microbiota. The establishment of a DR in a chronic manner also has an impact on the composition of the microbiota, which is more important in the early stages. Cumulatively, the results indicate that dietary restriction may be an optional approach for the treatment of colitis, alone or in combination with immunosuppressive agents, or as a rescue treatment for patients who do not respond or become less responsive to medical treatments.Parmi les symptômes les plus courants des maladies inflammatoires de l'intestin (MICI, qui comprennent la colite ulcéreuse et la maladie de Crohn) figurent les douleurs abdominales, la diarrhée et la perte de poids. Il n'est donc pas surprenant que les cliniciens et les patients se demandent si les habitudes alimentaires influencent l'apparition ou l'évolution des MICI. La question de l'alimentation est l'une des plus fréquemment posées par les patients et l'une des plus difficiles à résoudre pour les cliniciens. Des études récentes ont révélé que la restriction alimentaire est capable de moduler le système immunitaire et de contribuer à l'intervention dans les troubles immunitaires. Nous avons analysé ici l'effet thérapeutique de la restriction alimentaire (DR) intermittente personnalisé sur le modèle de MICI chronique induite par le sulfate de dextran sodique (DSS) chez la souris. Après avoir défini le pourcentage de restriction optimal, quatre cycles de DR ont été administrés avant l'apparition des symptômes des MICI chez les souris. L'administration de DR a réduit de manière significative le score de l'indice d'activité de la maladie. La DR a inversé le raccourcissement de la longueur du côlon induit par le DSS, le score endoscopique, la lipocaline fécale et améliore la perméabilité intestinale. L'expression d'un marqueur d'inflammation NLRP3 a également été réduite par l'administration de DR, tout en régulant le métabolisme des métabolites des monocarbones lié à l’activation de NLRP3. En outre, l'application de la DR à modifié l’expression local de cytokine pro et anti-inflammatoire, notamment IL-17a, IL-1β, IL-6 et INFγ. Les facteurs environnementaux, la perméabilité de la muqueuse et une immunorégulation défectueuse entraînent une immunité excessive à un sous-ensemble de bactéries intestinales résidentes qui médient de multiples conditions inflammatoires. La mise en place de la DR permet de réguler à la baisse le pouvoir pro-inflammatoire du microbiote. La mise en place d’une DR de manière chronique à également un impact sur la composition du microbiote, impact plus important dans les temps précoce. Dans l'ensemble, les résultats indiquent que la restriction alimentaire peut être une approche optionnelle pour le traitement de la colite , seuls ou en association avec des agents immunosuppresseurs, ou comme traitement de secours pour les patients qui ne répondent pas ou deviennent moins sensibles aux traitements médicaux

Telomeres: New players in immune-mediated inflammatory diseases?

International audienceTelomeres are repetitive DNA sequences located at the ends of linear chromosomes that preserve the integrity and stability of the genome. Telomere dysfunctions due to short telomeres or altered telomere structures can ultimately lead to replicative cellular senescence and chromosomal instability, both mechanisms being hallmarks of ageing. Chronic inflammation, oxidative stress and finally telomere length (TL) dynamics have been shown to be involved in various age-related non-communicable diseases (NCDs). Immune-mediated inflammatory diseases (IMIDs), including affections such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, spondyloarthritis and uveitis belong to this group of age-related NCDs. Although in recent years, we have witnessed the emergence of studies in the literature linking these IMIDs to TL dynamics, the causality between these diseases and telomere attrition is still unclear and controversial. In this review, we provide an overview of available studies on telomere dynamics and discuss the utility of TL measurements in immune-mediated inflammatory diseases

Calorie Restriction as a New Treatment of Inflammatory Diseases

International audienceImmoderate calorie intake coupled with a sedentary lifestyle are major determinants of health issues and inflammatory diseases in modern society.The balance between energy consumption and energy expenditure is critical for longevity. Excessive energy intake and adiposity cause systemicinflammation, whereas calorie restriction (CR) without malnutrition, exerts a potent anti-inflammatory effect. The objective of this review was toprovide an overview of different strategies used to reduce calorie intake, discuss physiological mechanisms by which CR might lead to improvedhealth outcomes, and summarize the present knowledge about inflammatory diseases. We discuss emerging data of observational studies andrandomized clinical trials on CR that have been shown to reduce inflammation and improve human health. Adv Nutr 2021;00:1–13

Sugars and Gastrointestinal Health

International audienc

Sugars and Gastrointestinal Health

Sugar overconsumption is linked to a rise in the incidence of noncommunicable diseases such as diabetes, cardiovascular diseases, and cancer. This increased incidence is becoming a real public health problem that is more severe than infectious diseases, contributing to 35 million deaths annually. Excessive intake of free sugars can cause many of the same health problems as excessive alcohol consumption. Many recent international recommendations have expressed concerns about sugar consumption in Westernized societies, as current consumption levels represent quantities with no precedent during hominin evolution. In both adults and children, the World Health Organization strongly recommends reducing free sugar intake to <10% of total energy intake and suggests a further reduction to below 5%. Most studies have focused on the deleterious effects of Western dietary patterns on global health and the intestine. Whereas excessive dietary fat consumption is well studied, the specific impact of sugar is poorly described, while refined sugars represent up to 40% of caloric intake within industrialized countries. However, high sugar intake is associated with multiple tissue and organ dysfunctions. Both hyperglycemia and excessive sugar intake disrupt the intestinal barrier, thus increasing gut permeability and causing profound gut microbiota dysbiosis, which results in a disturbance in mucosal immunity that enhances infection susceptibility. This review aims to highlight the roles of different types of dietary carbohydrates and the consequences of their excessive intake for intestinal homeostasis