Sabine Buhner

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (19)78.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Scope: Considering the increasing numbers of patients suffering from food allergy (FA) as well as the great variety of novel foods and food compositions, an unmet need exists for the development of preclinical approaches to characterize the allergenic potential of proteins. The aim of our study was to evaluate the allergenicity of different food allergens in a rat model. Methods: Brown Norway rats were sensitized to protein extracts (RuBisCO, apple, soy, peanut, garden pea) or ovalbumin (OVA) combined with Bordetella pertussis and aluminium hydroxide, followed by oral allergen challenges. Results: Allergen-specific serum immunoglobulin production and the proliferation of mononuclear cells from spleen confirmed sensitization. To assess functional alterations in the gut, intestinal permeability was measured, which increased in sensitized and challenged animals compared to non-sensitized controls. Allergens with high allergenic potential (peanut, OVA, soy) caused a stronger immunological response than allergens with low allergenic potential, such as RuBisCO and apple. Moreover, the immunological responses were reduced when using boiled instead of raw soy and pea proteins. Conclusion: This model mimics key features of FA and facilitates investigating the allergenicity of allergens in novel food or food compositions in vivo. © 2014 S. Karger AG, Basel.
    International archives of allergy and immunology. 06/2014; 164(2):89-96.
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    ABSTRACT: Modulating early immune response by application of bacteria and their by-products has been suggested as a preventive strategy against the development of allergic diseases. In light of this, the aim of the study was to test the effects of oral administration of bacterial lysates (BL) in a rat model of food allergy. BL or PBS were administered orally to neonatal Brown Norway rats up to an age of 42 days. Additionally, animals were sensitized 3 times (days 35, 40 and 45) intraperitoneally with ovalbumin (OVA). On days 60 and 61, rats were locally challenged with OVA by gavage feeding. Detection of increased allergen-specific Ig serum levels and proliferative responses of spleen mononuclear cells confirmed systemic sensitization. In serum of animals that received BL in addition to OVA sensitization, the levels of allergen-specific IgE and IgG were significantly reduced compared to animals which were not exposed to BL. Allergen-stimulated lymphocytes from spleen and mesenteric lymph nodes of BL-treated animals showed a significantly elevated cytokine production of IL-10. To assess local functional changes of the intestinal barrier we measured the intestinal permeability, which was increased in OVA-sensitized and challenged animals compared to nonsensitized controls, yet significantly reduced in sensitized animals which received BL. These data suggest that local administration of BL (pathogen-associated molecular patterns) in the intestine exhibits immuno-modulating effects. Furthermore, pathophysiological features of food allergy, such as the loss of gut mucosal integrity, might be reduced by the treatment with BL.
    International Archives of Allergy and Immunology 05/2011; 156(2):196-204. · 2.25 Impact Factor
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    ABSTRACT: Small intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF. We measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation. CHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p<0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2±2.0% vs. 20.8±2.4% vs. 36.0 ± 3.7%, all p ≤ 0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p=0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p=0.004). Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of TNF (7.0 ± 1.6 vs. 3.1 ± 0.3pg/mL, p<0.02), and sTNF-R1 (3499 ± 52 vs. 1599±219 pg/mL, p=0.02). Active carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.
    International journal of cardiology 12/2010; 157(1):80-5. · 7.08 Impact Factor
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    ABSTRACT: Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups. After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG). In controls, sucralose excretion was highly variable (0.67+/-0.92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0.054+/-0.060; 0.323+/-0.253 vs. 0.018+/-0.001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG (r=0.72, and r=0.51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients (P=0.099), sucralose excretion was not related to clinical outcome. The proposed cut-off for normal sucralose excretion is 2.11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.
    European Journal of Clinical Investigation 03/2009; 39(2):139-44. · 3.37 Impact Factor
  • Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor
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    ABSTRACT: The pain intensity of patients with FM has recently been reported to be correlated with the degree of small intestinal bacterial overgrowth (SIBO). SIBO is often associated with an increased intestinal permeability (IP). Increased IP, if shown in FM, may have pathogenetic relevance because it leads to the exposure of immune cells to luminal antigens and consequent immune modulation. It is currently unknown whether IP is altered in FM. We therefore examined the IP in a group of patients with primary FM and in two control groups, healthy volunteers and patients with an unrelated chronic pain syndrome, complex regional pain syndrome (CRPS). We hypothesized that patients with FM, but not volunteers or those patients with CRPS, would have altered IP. Both gastroduodenal and small IP were assessed using an established three-sugar test, where urinary disaccharide excretion reflecting intestinal uptake was measured using HPLC. Forty patients with primary FM, 57 age- and sex-matched volunteers and 17 patients with CRPS were enrolled in this study. In the FM group, 13 patients had raised gastroduodenal permeability and 15 patients had raised small intestinal permeability, but only one volunteer had increased gastroduodenal permeability (P < 0.0001, chi-square test for the three groups). The IP values were significantly increased in the patient groups (P < 0.0003 for all comparisons, one-way analysis of variance). The IPs in primary FM and, unexpectedly, CRPS are increased. This study should stimulate further research to determine the implication of altered IP in the disease pathophysiology of FM and CRPS.
    Rheumatology (Oxford, England) 09/2008; 47(8):1223-7. · 4.24 Impact Factor
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    ABSTRACT: Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls. Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile]. Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease. This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.
    Clinical nutrition (Edinburgh, Scotland) 04/2008; 27(4):571-8. · 3.27 Impact Factor
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    ABSTRACT: This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.
    Nutrition 01/2008; 24(7-8):694-702. · 2.86 Impact Factor
  • Clinical Nutrition Supplements 01/2008; 3:14-14.
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    ABSTRACT: A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n=310; ulcerative colitis [UC] n=179), Hungary (CD n=147; UC n=117), and the Netherlands (CD n=157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics. We found a highly significant association of c.898A>G to CD. The association was significant (p=0.0005) for the total CD cohort but also for the individual populations from Germany (p=0.02) and Netherlands (p=0.02) whereas in the Hungarian CD patients a clear trend was observed (p=0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and CARD15 variants. Furthermore no association to a CD subphenotype was detected. We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype.
    Journal of Crohn s and Colitis 12/2007; 1(2):70-6. · 3.39 Impact Factor
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    ABSTRACT: We evaluated morphology and function of the gut in patients with chronic heart failure (CHF). Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal. We studied 22 patients with CHF (age 67 +/- 2 years, left ventricular ejection fraction [LVEF] 31 +/- 1%, New York Heart Association functional class 2.3 +/- 0.1, peak VO2 15.0 +/- 1.0 ml/kg/min) and 22 control subjects (62 +/- 1 years, LVEF 68 +/- 2%, peak VO2 24.7 +/- 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy. Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 +/- 0.16 mm vs. 1.04 +/- 0.08 mm), ascending colon (2.32 +/- 0.18 mm vs. 1.31 +/- 0.14 mm), transverse colon (2.19 +/- 0.20 vs. 1.27 +/- 0.08 mm), descending colon (2.59 +/- 0.18 mm vs. 1.43 +/- 0.13 mm), and sigmoid (2.97 +/- 0.27 mm vs. 1.64 +/- 0.14 mm) (all p < 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 +/- 0.001 vs. 0.017 +/- 0.001, p = 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 +/- 0.17% vs. 0.20 +/- 0.06%, p = 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 +/- 3.0% vs. 37.4 +/- 1.4%, p = 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p = 0.007). Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.
    Journal of the American College of Cardiology 10/2007; 50(16):1561-9. · 14.09 Impact Factor
  • European Journal of Heart Failure Supplements 01/2007; 6(1):85-85.
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    ABSTRACT: We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.
    The Journal of international medical research 01/2007; 35(1):72-83. · 0.96 Impact Factor
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2007; 45(08).
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    ABSTRACT: Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD). Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test. Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability. We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.
    The American Journal of Gastroenterology 05/2006; 101(4):786-92. · 7.55 Impact Factor
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    ABSTRACT: A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.
    Gut 04/2006; 55(3):342-7. · 10.73 Impact Factor
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    ABSTRACT: In a subgroup of patients with chronic urticaria (CU) the disease is caused by pseudoallergic reactions to food. The aim of this study was to investigate whether disturbances of the gastrointestinal barrier function play a role in the pathomechanism of the disease. In 55 patients with CU gastrointestinal permeability was measured with an in vivo triple-sugar-test before and after 24 days of a diet low in pseudoallergens. Sucrose served as marker for gastroduodenal permeability, lactulose/mannitol ratio for intestinal permeability. Basal gastroduodenal and intestinal permeability were significantly higher in patients with urticaria as compared to controls. In 29 of the 55 patients skin symptoms decreased or completely disappeared during the diet (responders). Compared to nonresponders (n = 26), responders had a significantly higher gastroduodenal permeability before treatment (0.36 +/- 0.04 vs 0.15 +/- 0.01% sucrose; P < 0.001), which decreased after the diet (0.17 +/- 0.02; P < 0.001). The number of patients with Helicobacter pylori infections did not differ between the two groups. The results indicate that in a subgroup of patients with CU and pseudoallergy an impaired gastroduodenal barrier function may be of pathophysiological importance. The underlying mechanisms seem to be independent of H. pylori infection.
    Allergy 10/2004; 59(10):1118-23. · 5.88 Impact Factor