Yurdagül Zopf

In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease

As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohns disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohns disease led to detection of intestinal mTNF+ immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF+ cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF+ cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohns disease and autoimmune or inflammatory disorders.

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.

Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study

BACKGROUND AND STUDY AIM The differential diagnosis of ulcerative colitis from Crohns disease is of pivotal importance for the management of inflammatory bowel diseases, as both entities involve specific therapeutic management strategies. Confocal laser endomicroscopy (CLE) allows on-demand, in vivo characterization of architectural and cellular details during endoscopy. The aim of this study was to assess the efficacy of CLE to differentiate between ulcerative colitis and Crohns disease. PATIENTS AND METHODS This was a prospective study involving consecutive patients with a well-established diagnosis of ulcerative colitis or Crohns disease who underwent colonoscopy with fluorescein-aided confocal imaging. RESULTS Overall, 79 patients were included (40 Crohns disease, 39 ulcerative colitis). CLE findings in patients with Crohns disease, showed significantly more discontinuous inflammation (87.5 % vs. 5.1 %), focal cryptitis (75.0 % vs. 12.8 %), and discontinuous crypt architectural abnormality (87.5 % vs. 10.3 %) than in ulcerative colitis (P < 0.0001). Conversely, ulcerative colitis was associated with severe, widespread crypt distortion (87.2 % vs. 17.5 % in Crohns disease), decreased crypt density (79.5 % vs. 22.5 %), and frankly irregular surface (89.7 % vs. 17.5 %; P < 0.0001 for all comparisons). Statistically significant differences were not seen for heavy, diffuse lamina propria cell increase or mucin preservation. No granulomas were visible. Based on these findings, a CLE scoring system was developed that revealed excellent accuracy (93.7 %) when compared with the historical clinical diagnosis and the histopathological gold standard. CONCLUSIONS CLE could visualize several disease-specific microscopic features, which are conventionally used in standard histopathology to differentiate between ulcerative colitis and Crohns disease. However, because of the limited penetration depth of CLE, submucosal details or granulomas were not visible. The new scoring system may allow in vivo diagnosis of ulcerative colitis or Crohns disease. Trial registered at ClinicalTrials.gov: NCT 02238665.

Malnutrition in Hospitals: It Was, Is Now, and Must Not Remain a Problem!

Background Malnutrition is an under-recognized problem in hospitalized patients. Despite systematic screening, the prevalence of malnutrition in the hospital did not decrease in the last few decades. The aim of our study was to evaluate the prevalence of malnutrition and to determine the explicit daily calorie intake of hospitalized patients, to identify the risk factors of developing malnutrition during hospitalization and the effect on the financial reimbursement according to the German DRG-system. Material/Methods 815 hospitalized patients were included in this study. The detection of malnutrition was based on the nutritional-risk-screening (NRS) and subjective-global-assessment (SGA) scores. A trained investigator recorded the daily calorie and fluid intake of each patient. Furthermore, clinical parameters, and the financial reimbursement were evaluated. Results The prevalence of malnutrition was 53.6% according to the SGA and 44.6% according the NRS. During hospitalization, patients received on average 759.9±546.8 kcal/day. The prevalence of malnutrition was increased in patients with hepatic and gastrointestinal disease and with depression or dementia. The most important risk factors for malnutrition were bed rest and immobility (OR=5.88, 95% CI 2.25–15.4). In 84.5% of patient records, malnutrition was not correctly coded, leading to increased financial losses according to the DRG-system (94.908 Euros). Conclusions Hospitalized patients suffer from inadequate nutritional therapy and the risk for developing malnutrition rises during the hospital stay. The early screening of patients for malnutrition would not only improve management of nutritional therapy but also, with adequate coding, improve financial reimbursement according to the DRG-system.

Small-bowel capsule endoscopy in patients with gastrointestinal food allergy.

To cite this article: Hagel AF, de Rossi TM, Zopf Y, Lindner AS, Dauth W, Neurath MF, Raithel M. Small‐bowel capsule endoscopy in patients with gastrointestinal food allergy. Allergy 2012; 67: 286–292.

Influence of low FODMAP and gluten-free diets on disease activity and intestinal microbiota in patients with non-celiac gluten sensitivity

BACKGROUND & AIMS Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms triggered by ingestion of gluten. However, non-gluten triggers have recently been implicated, and a FODMAP (fermentable oligo-, di-, monosaccharides and polyols)-reduced diet can partially improve symptoms in NCGS. Our aim was to analyze the effect of a low FODMAP versus a gluten-free diet (GFD) on clinical symptoms, psychological well-being, intestinal inflammation and integrity, and stool microbiota. METHODS Nineteen patients with NCGS and ten healthy controls consumed a gluten-containing standard diet before starting a two-week low FODMAP diet; after a five day transition period, participants ingested a GFD for another two weeks. The primary outcome measure was the improvement of clinical symptoms in NCGS patients under the different diets. Secondary outcomes were the determination of dietary effects on intestinal inflammation, psychological well-being, and differences in stool microbiota between NCGS patients and controls. RESULTS The low FODMAP diet and especially the GFD led to a significant improvement of clinical and psychological symptoms in NCGS. A clear reduction in duodenal intraepithelial lymphocytes and mucin-producing Goblet cells was found after the GFD in these patients. Significant microbial differences between NCGS patients and controls were noticed in stool samples at every time point. Both diets caused microbial shifts in all participants, with a greater variability on genus level and metabolisms groups in NCGS patients. CONCLUSIONS Our findings suggest a multifactorial etiology of NCGS, due to a functional effect caused by FODMAPs, combined with a mild gluten-triggered immune reaction, and a microbiota dysbalance. CLINICALTRIAL. GOV ID NCT03268720.

Therapeutische Modulation der Darmmikrobiota beim Reizdarmsyndrom

ZusammenfassungHintergrundEine gestörte Darmmikrobiota (Dysbiose) spielt eine zentrale Rolle in der Pathogenese funktioneller Darmerkrankungen, insbesondere des Reizdarmsyndroms.MethodeIn der Übersichtsarbeit sind vier derzeitige Optionen zur Behandlung des Reizdarmsyndroms dargestellt, die über eine Modulation der Darmmikrobiota wirken.Ergebnisse und SchlussfolgerungenProbiotika wirken sehr unterschiedlich auf die einzelnen Symptome des Reizdarms. Die Wahl des geeigneten Präparats sollte sich deshalb nach den klinischen Symptomen richten. Rifaximin ist bei ausgewählten Patienten wirksam. Einige Patienten profitieren auch von der Wiederholung dieser Antibiotikatherapie. Eine FODMAP-reduzierte Diät hat in Studien eine signifikante Linderung der Reizdarmsymptome gezeigt. Die fäkale Mikrobiota-Therapie (FMT) ist eine vielversprechende Behandlungsmöglichkeit. Derzeit fehlen allerdings entsprechende placebokontrollierte Studien, um die engültige Wirksamkeit dieser Methode beurteilen zu können.AbstractBackgroundAn abnormal intestinal microbiota (dysbiosis) plays a central role in the pathogenesis of the irritable bowel syndrome.MethodAn overview of four current options for the treatment of irritable bowel syndrome, which are characterized by modulation of intestinal microbiota, is given.Results and conclusionsProbiotics have very different effects on the individual symptoms of the irritable bowel. The choice of the appropriate preparation should therefore be based on the clinical symptomatology. The antibiotic rifaximin is effective in selected patients. Some patients also benefit from the repetition of this therapy. A FODMAP-reduced diet has shown significant alleviation of irritable bowel symptoms in studies. The fecal microbiota therapy (FMT) is a promising treatment option. At present, however, there are no such placebo-controlled studies to assess the effectiveness of this method.BACKGROUND An abnormal intestinal microbiota (dysbiosis) plays a central role in the pathogenesis of the irritable bowel syndrome. METHOD An overview of four current options for the treatment of irritable bowel syndrome, which are characterized by modulation of intestinal microbiota, is given. RESULTS AND CONCLUSIONS Probiotics have very different effects on the individual symptoms of the irritable bowel. The choice of the appropriate preparation should therefore be based on the clinical symptomatology. The antibiotic rifaximin is effective in selected patients. Some patients also benefit from the repetition of this therapy. A FODMAP-reduced diet has shown significant alleviation of irritable bowel symptoms in studies. The fecal microbiota therapy (FMT) is a promising treatment option. At present, however, there are no such placebo-controlled studies to assess the effectiveness of this method.

Nicht-Zöliakie-Nicht-Weizenallergie-Weizensensitivität

Non-celiac non-wheat allergy wheat sensitivity is regarded as discrete glutensensitivity diagnosed after the exclusion of celiac disease and wheat allergy. Due to the absence of reliable biomarkers no exact prevalence rates are known and estimations range between 0,5-6 %. Soon after ingestion of wheat, patients complain of intestinal symptoms mainly bloating, abdominal pain, diarrhea or nausea which improve fast under glutenfree diet. Often extraintestinal manifestation as tiredness, muscle or joint pain, headache and depression are reported. Actually, there are no serological markers and no intestinal mucosal damage was found in patients. The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers. In addition, the involvement of the intestinal microbiome in pathology of glutensensitivity must be considered.

Leber-Darm-Achse: Wie Darmbakterien die Leber beeinflussen

ZusammenfassungHintergrundLeber und Darm stehen in engem Austausch miteinander. Das Risiko für eine Schädigung der Leber steigt, wenn die Darmbarriere geschädigt ist („leaky gut“).MethodeIn der Übersichtsarbeit wird dargestellt, wie Darmbakterien die Pathogenese chronischer Lebererkrankungen beeinflussen und welche Therapiemöglichkeiten es gibt.Ergebnisse und SchlussfolgerungenDie Dysbiose im Darm spielt eine wichtige Rolle bei der Entstehung chronischer Lebererkrankungen wie der alkoholischen Leberkrankheit, der nichtalkoholischen Fettlebererkrankung, der primär biliären Cholangitis, der primär sklerosierenden Cholangitis und der Leberzirrhose. Eine Darmmikrobiom-modulierende Therapie mit Probiotika, Prebiotika oder Synbiotika zeigt positive Effekte. Die genauere Bedeutung dieses Therapieansatzes müssen weitere Studien klären.AbstractBackgroundLiver and intestine are in close contact with each other. The risk of damage to the liver increases, when the intestinal barrier is damaged (“leaky gut”) .MethodThe review article describes how intestinal bacteria influence the pathogenesis of chronic liver diseases and what treatment options are available.Results and ConclusionsIntestinal dysbiosis plays an important role in the development of chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and cirrhosis. Intestinal microbial modulating therapy with probiotics, prebiotics or synbiotics shows positive effects. The more precise meaning of this therapeutic approach needs to be clarified in further studies.

Dietary Effects on Microbiota—New Trends with Gluten-Free or Paleo Diet

A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, largely associated with dramatic changes in food consumption trends and main nutrients. A major response to food intolerances has been the adoption of new dietary trends involving the reduction or exclusion of specific food ingredients. Especially gluten-containing, but also gluten-free cereals are in the cross-fire. Supporters of the gluten-free diet argue that gluten triggers inflammation and related diseases, while followers of the Paleo diet drastically impeach all cereals as dangerous for human health. To date, no controlled studies support or reject a positive health effect of a gluten-free or cereal-free diet. Future large-scale studies need to evaluate the effect of gluten-containing and gluten-free cereals and the various diets on human health, inflammatory parameters, clinical symptoms, and the gut microbiota (including the bacteria, fungi, and viruses). Dietary-associated changes in compositional and functional microbiota traits should be correlated with the health status for the future development of dietary recommendations and potential clinical interventions.