ESPEN Guideline: Clinical Nutrition in inflammatory bowel disease

Introduction: The ESPEN guideline presents a multidisciplinary focus on clinical nutrition in inflammatory bowel disease (IBD). Methodology: The guideline is based on extensive systematic review of the literature, but relies on expert opinion when objective data were lacking or inconclusive. The conclusions and 64 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. Results: IBD is increasingly common and potential dietary factors in its aetiology are briefly reviewed. Malnutrition is highly prevalent in IBD – especially in Crohn's disease. Increased energy and protein requirements are observed in some patients. The management of malnu-trition in IBD is considered within the general context of support for malnourished patients. Treatment of iron deficiency (parenterally if necessary) is strongly recommended. Routine provision of a special diet in IBD is not however supported. Parenteral nutrition is indicated only when enteral nutrition has failed or is impossible. The recommended perioperative man-agement of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery. Probiotics may be helpful in UC but not Crohn's disease. Primary therapy using nutrition to treat IBD is not supported in ulcerative colitis, but is mod-erately well supported in Crohn's disease, especially in children where the adverse conse-quences of steroid therapy are proportionally greater. However, exclusion diets are generally not recommended and there is little evidence to support any particular formula feed when nutritional regimens are constructed. Conclusions: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 64 recommendations, of which 9 are very strong recom-mendations (grade A), 22 are strong recommendations (grade B) and 12 are based only on sparse evidence (grade 0); 21 recommendations are good practice points (GPP)

L-Threonine Supplementation During Colitis Onset Delays Disease Recovery

Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most adequate phase of action. To unveil the most prominent therapy candidates we characterized the colon metabolic profile during colitis development. We have observed a twofold decrease in threonine levels in mice subjected to DSS-induced colitis. We then assessed the effect of threonine supplementation in the beginning of the inflammatory process (DSS + Thr) or when inflammation is already established (DSS + Thr D8). Colitis progression was similar between the treated groups and control colitic mice, yet threonine had a surprisingly detrimental effect when administered in the beginning of the disease, with mice displaying a delayed recovery when compared to control mice and mice supplemented with threonine after day 8. Although no major changes were found in their metabolic profile, DSS + Thr mice displayed altered expression in mucin-encoding genes, as well as in goblet cell counts, unveiling an impaired ability to produce mucus. Moreover, IL-22 secretion was decreased in DSS + Thr mice when compared to DSS + Thr D8 mice. Overall, these results suggest that supplementation with threonine during colitis induction impact goblet cell number and delays the recovery period. This reinforces the importance of a deeper understanding regarding threonine supplementation in IBD.Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) and the Fundação para a Ciência e Tecnologia (FCT) (contracts PD/BD/106053/2015 to JG via Inter-University Doctoral Programme in Ageing and Chronic Disease – PhDOC, IF/00021/2014 to RS, IF/01390/2014 to ET, IF/01147/2013 to RD-O, IF/00735/2014 to AgC, SFRH/BPD/96176/2013 to CC, and SFRH/BPD/111100/2015 to LG). MS is a FCT investigator. The NMR data was acquired at CERMAX (Centro de Ressonância Magnética António Xavier) which is a member of the National NMR network with the support of Project LISBOA-01-0145-FEDER-007660info:eu-repo/semantics/publishedVersio

The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis

BACKGROUND: Accurate measurement of renal function in cirrhotic patients is still challenging. To find the best test for the determination of the true glomerular filtration rate (GFR) in cirrhotic patients this study prospectively compared measured (m)GFR, the gold standard, with estimated (e)GFR using equations based on serum levels of creatinine and cystatin C. METHODS: GFR was measured by sinistrin clearance using the bolus method in 50 patients with cirrhosis (Child Turcotte Pugh score A, B and C) and 24 age-matched healthy subjects as controls. Measured (m)GFR was compared to eGFR using bias, accuracy 10 % and 30 %, as well as correlation coefficients. RESULTS: Creatinine-based equations generally overestimated GFR in patients with cirrhosis and showed a bias (average difference between mGFR and eGFR) of −40 (CG), −12 (MDRD) and −9 (CKD-EPI-Cr) ml/min/1.73 m(2). Cystatin C-based equations underestimated GFR, especially in patients with Child Turcotte Pugh score C (bias 17 ml/min/1.73 m(2)for CKD-EPI-CysC). Of these equations, the CKD-EPI equation that combines creatinine and cystatin C (CKD-EPI-Cr-CysC) showed a bias of 0.12 ml/min/1.73 m(2) as compared to measured GFR. CONCLUSIONS: The CKD-EPI equation that combines serum creatinine and cystatin C measurements shows the best performance for accurate estimation of GFR in cirrhosis, especially at advanced stages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-015-0188-0) contains supplementary material, which is available to authorized users

Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis

IntroductionEosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing.MethodsIn this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus.ResultsOur results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE.DiscussionHerein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models