Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a group of debilitating disorders affecting patient’s quality of life and with unknown aetiology. The collected evidence indicates that individuals can develop IBD as a result of genetic susceptibility, a dysregulated immune response and the influence of certain environmental factors. Common symptomatology includes abdominal pain, fever and bowel diarrhoea with blood and/or mucus excretion. The location and extent of disease differ between UC and CD, affecting the mucosal layer in the colon in UC patients, whereas in CD patients, a transmural inflammation is found anywhere in the gastrointestinal tract. Factors associated with IBD pathophysiology include alterations in immune responses, characterized by an atypically T helper (Th)-2 profile in UC, and a Th1/Th17 profile in CD, modifications in epithelial barrier function and alterations in the commensal microbiota composition with blooming of specific pathobionts, for example, adherent-invasive Escherichia coli (AIEC), and with diet. Recent research has uncovered that inflammation, per se, can activate the enteric nervous system inducing neurogenic inflammation and increasing visceral sensitivity, leading to pain. Similarly, alterations in the commensal microbiota composition/ligands have also led to modifications in intestinal nociceptive markers and in visceral pain. In this chapter, we aim to review the mechanisms implicated in microbial neuro-immune axis and its potential contribution to IBD pathophysiology and symptomatology. We focus on the findings identified in animal models and in IBD patients and on the prospective translation of targeting the microbial neuro-immune axis as future therapeutic treatment for intestinal inflammatory conditions

Modelling of Mouse Experimental Colitis by Global Property Screens: A Holistic Approach to Assess Drug Effects in Inflammatory Bowel Disease

Preclinical disease models play an important role in the establishment of new treatment paradigms, identification of biomarkers and assessment of drug efficacy and safety. However, the accuracy of these models in context of the human disease are sometimes questioned, e.g. due to trials failing to confirm efficacy in humans. We suggest that one reason behind this gap in predictability may relate to how the preclinical data is analyzed and interpreted. In the present paper, we introduce a holistic approach to analyze and illustrate data in context of one of the most commonly used colitis models, i.e. the mouse dextran sulphate sodium (DSS) colitis model. Diseased mice were followed over time along disease progression and by use of tool pharmacological compounds activating nuclear hormone receptors, respectively. A new multivariate statistics approach was applied including principal component analysis (PCA) with treatment prediction subsequent to establishing the principal component analysis model. Thus, several studies could be overlaid and compared to each other in a new, comprehensive and holistic way. This method, named mouse colitis global property screening, appears applicable not only to any animal modelling series of studies but also to human clinical studies. The prerequisites for the study set up and calculations are delineated and examples of new learnings from the global property screening will be presented

Emerging applications of upconverting nanoparticles in intestinal infection and colorectal cancer

Colorectal cancer is the abnormal growth of cells in colon or rectum. Recent findings have acknowledged the role of bacterial infection and chronic inflammation in colorectal cancer initiation and progression. In order to detect and treat precancerous lesions, new tools are required, which may help to prevent or identify colorectal cancer at an early stage. To date, several different screening tests are available, including endoscopy, stool-based blood tests, and radiology-based tests. However, these analyses either lack sensitivity or are of an invasive nature. The use of fluorescently labeled probes can increase the detection sensitivity. However, autofluorescence, photobleaching, and photodamage are commonly encountered problems with fluorescence imaging. Upconverting nanoparticles (UCNPs) are recently developed lanthanide-doped nanocrystals that can be used as light-triggered luminescent probes and in drug delivery systems. In this review, we comprehensively summarize the recent developments and address future prospects of UCNP-based applications for diagnostics and therapeutic approaches associated with intestinal infection and colorectal cancer

The impact of western diet and nutrients on the microbiota and immune response at mucosal interfaces

Recent findings point toward diet having a major impact on human health. Diets can either affect the gut microbiota resulting in alterations in the host's physiological responses or by directly targeting the host response. The microbial community in the mammalian gut is a complex and dynamic system crucial for the development and maturation of both systemic and mucosal immune responses. Therefore, the complex interaction between available nutrients, the microbiota, and the immune system are central regulators in maintaining homeostasis and fighting against invading pathogens at mucosal sites. Westernized diet, defined as high dietary intake of saturated fats and sucrose and low intake of fiber, represent a growing health risk contributing to the increased occurrence of metabolic diseases, e.g., diabetes and obesity in countries adapting a westernized lifestyle. Inflammatory bowel diseases (IBD) and asthma are chronic mucosal inflammatory conditions of unknown etiology with increasing prevalence worldwide. These conditions have a multifactorial etiology including genetic factors, environmental factors, and dysregulated immune responses. Their increased prevalence cannot solely be attributed to genetic considerations implying that other factors such as diet can be a major contributor. Recent reports indicate that the gut microbiota and modifications thereof, due to a consumption of a diet high in saturated fats and low in fibers, can trigger factors regulating the development and/or progression of both conditions. While asthma is a disease of the airways, increasing evidence indicates a link between the gut and airways in disease development. Herein, we provide a comprehensive review on the impact of westernized diet and associated nutrients on immune cell responses and the microbiota and how these can influence the pathology of IBD and asthma

Shining a Light on Intestinal Traffic

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is associated with enhanced leukocyte infiltration to the gut, which is directly linked to the clinical aspects of these disorders. Thus, leukocyte trafficking is a major target for IBD therapy. Past and emerging techniques to study leukocyte trafficking both in vitro and in vivo have expanded our knowledge of the leukocyte migration process and the role of inhibitors. Various strategies have been employed to target chemokine- and integrin-ligand interactions within the multistep adhesion cascade and the S1P/S1PR1 axis in leukocyte migration. Though there is an abundance of preclinical data demonstrating efficacy of leukocyte trafficking inhibitors, many have yet to be confirmed in clinical studies. Vigilance for toxicity and further research is required into this complex and emerging area of IBD therapy

Caracterización física de los residuos sólidos de la Facultad Multidisciplinaria Oriental, Universidad de El Salvador, 2012.

El estudio de la caracterización física de los residuos sólidos de la Facultad Multidisciplinaria Oriental (F.M.O), está enmarcado dentro de los Fines de la Universidad de El Salvador que establecen su compromiso en conservar, fomentar y difundir la ciencia, promoviendo la sustentabilidad y la protección de los recursos naturales y el medio ambiente. Así también, el manejo integral de los residuos sólidos se ha vuelto una necesidad para todas las autoridades municipales en el país al entrar en vigencia la Ley del Medio Ambiente que manifiesta la obligación de presentar diagnósticos ambientales de los sitios de disposición final de los residuos sólidos, además, el Reglamento especial de manejo integral de desechos sólidos señala la obligación de contar con sistemas integrales para la gestión de los mismos. La metodología descriptiva, utilizada en la investigación, permitió especificar las propiedades importantes de la caracterización física de residuos sólidos en la F.M.O. Para ello, se incluyeron las variables cualitativas (componentes de los residuos sólidos) y cuantitativas (peso, volumen y densidad); se incluyó la metodología exploratoria, que fue de utilidad porque la temática estudiada no ha sido investigada por otros autores de forma exhaustiva. Los resultados obtenidos según análisis de varianza, muestran que hay diferencia significativa entre al menos uno de los componentes de los residuos sólidos, estableciéndose diferencia significativa entre el plástico con un promedio de 71.98 kgs. y los residuos de comida con un promedio de 81.74 kgs. tienen diferencia significativa con todos los demás componentes de los residuos sólidos de la F.M.O., siendo por tanto planteadas en esta investigación alternativas de tratamiento para los residuos de comida y plástico

Research gaps in diet and nutrition in inflammatory bowel disease. A topical review by D-ECCO Working Group (Dietitians of ECCO)

Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors with gut microbiota in genetically-susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarized collectively under three main thematic domains: i) the role of diet as an environmental factor in IBD aetiology; ii) the role of diet as induction and maintenance therapy in IBD; and iii) assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed which is anticipated to be agenda setting for future research in the area of diet and nutrition in IBD