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1.
Front Immunol ; 15: 1347259, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38318168

RESUMEN

Introduction: Eosinophilic 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. Methods: In 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. Results: Our 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. Discussion: Herein 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.


Asunto(s)
Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Reflujo Gastroesofágico , Animales , Ratones , Humanos , Esofagitis Eosinofílica/diagnóstico , Leucocitos Mononucleares/metabolismo , Receptor de Muerte Celular Programada 1 , Proteómica , Membrana Mucosa/metabolismo , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/patología
2.
Inflamm Bowel Dis ; 30(1): 9-19, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37463118

RESUMEN

BACKGROUND: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.


Asunto(s)
Colitis Ulcerosa , Humanos , Colitis Ulcerosa/terapia , ARN Ribosómico 16S/genética , Estudios Prospectivos , Heces/microbiología , Corticoesteroides/uso terapéutico , Resultado del Tratamiento
3.
J Clin Med ; 12(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37510968

RESUMEN

BACKGROUND: Among patients with ulcerative colitis, 30-50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. RESULTS: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. CONCLUSION: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

4.
Dig Dis ; 41(3): 387-395, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36412565

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.


Asunto(s)
Productos Biológicos , COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Europa (Continente)/epidemiología , Encuestas y Cuestionarios
5.
Cells ; 11(21)2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36359859

RESUMEN

Hematopoietic stem cell transplantation (HSCT) is widely used in benign and malignant hematological diseases. During the last decade, HSCT, mainly autologous, also gained increasing attention in the treatment of refractory autoimmune diseases. Crohn's disease (CD) is an inflammatory bowel disease leading to transmural inflammation potentially affecting all parts of the luminal gastrointestinal tract. Despite improving therapeutic options, including various biologics, some patients are refractory to all lines of available conservative therapy, leading to increased morbidity and reduced quality of life. Apart from surgery, HSCT might be a reasonable treatment alternative for refractory CD patients. This review aims to describe the current role of HSCT in CD and discusses the procedure, the correct patient selection, the clinical efficacy from initial remission to following relapse rates, and complications of this treatment.


Asunto(s)
Enfermedad de Crohn , Trasplante de Células Madre Hematopoyéticas , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedad de Crohn/terapia , Calidad de Vida , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Autólogo , Enfermedades Inflamatorias del Intestino/etiología , Enfermedad Crónica
6.
Scand J Gastroenterol ; 57(11): 1327-1330, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35732583

RESUMEN

BACKGROUND AND AIMS: Immunological treatment failure of anti-TNF therapy negatively influences treatment persistence of a second anti-TNF in IBD patients. So far it is unknown if this effect is also observed for other monoclonal antibodies. We assessed the influence of immunogenicity to anti-TNFs on treatment persistence of subsequent ustekinumab and vedolizumab therapy. METHODS: IBD patients with and without immunogenicity to anti-TNFs (undetectable trough levels and antibody titers ≥20 ng/mL) and subsequent ustekinumab (UST) and/or vedolizumab (VDZ) therapy were included in this retrospective, single-center study. The Kaplan-Meier method with the log-rank test and Cox proportional hazards were used as statistical methods. RESULTS: One hundred patients (Crohn's disease: 62, Ulcerative colitis: 31, IBD unclassified: 7) with 127 treatment lines (62 with UST, 65 with VDZ) were included in the analysis. Immunogenicity to previous anti-TNFs did not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy (UST: Log rank: p = .95, Immunogenicity: HR for treatment discontinuation: 0.97 [95% CI 0.31-3.04]; VDZ: p = .65, HR: 0.85 [0.41-1.75]; total cohort [UST and VDZ]: p = .62, HR: 0.86 [0.47-1.57]). Azathioprine co-treatment did not lengthen treatment persistence (UST: Log rank: p = .77, azathioprine: HR: 1.20 [0.34-4.27]; VDZ: p = .92, HR: 0.58 [0.17-1.99]; total cohort: p = .79, HR: 1.10 [0.55-2.20]). In this anti-TNF experienced cohort, patients with ustekinumab remained longer on treatment than patients receiving vedolizumab (Log rank: p = .005, UST: HR: 0.43 [0.23-0.79]). CONCLUSIONS: Immunogenicity to anti-TNFs does not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Ustekinumab , Humanos , Ustekinumab/uso terapéutico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral , Fármacos Gastrointestinales/uso terapéutico , Azatioprina/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Resultado del Tratamiento
8.
Aliment Pharmacol Ther ; 54(5): 667-677, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34151449

RESUMEN

BACKGROUND: Anti-TNF antibodies were the first biologic treatment option for patients with inflammatory bowel diseases. AIMS: To assess length of treatment persistence of first anti-TNF therapy and influencing factors used in the standard care of patients with inflammatory bowel diseases. METHODS: Single-centre, retrospective study from a register including patients who received anti-TNF therapy in the last 20 years at the study centre. Kaplan-Meier analysis with log-rank test was used to describe treatment persistence. With multivariable Cox regression analysis, risk factors for treatment failure were investigated. RESULTS: Five hundred thirty-eight patients (CD, Crohn's disease: 367, UC, ulcerative colitis: 147, inflammatory bowel disease unclassified: 24) with a median follow-up of 8.1 years were included. Median (95% confidence interval) treatment persistence in the total cohort was 2.3 years (28 [22, 38] months), and nearly half of patients withdrew from treatment within 2 years. Male patients were treated longer than females (male: 37 [25, 48] months, female: 23 [14, 33] months, P = 0.002). Treatment persistence was longer in CD compared to UC (CD: 39 [30, 50] months, UC: 13 [9, 19] months, P < 0.001), and patients with CD remained longer on adalimumab than on infliximab treatment (adalimumab: 67 [55, 95] months, infliximab: 19 [14, 31] months, P < 0.001). Treatment failure (52%) and side effects (25%) were the most common reasons for withdrawal from therapy; 14% withdrew due to remission. Female sex was identified as independent predictor for treatment failure in UC (hazard ratio [CI]: 1.73 [1.02-2.92], P = 0.04). CONCLUSION: Long-term treatment persistence of first anti-TNF therapy was limited in patients with inflammatory bowel diseases, primarily due to treatment failure and side effects.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adalimumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Masculino , Estudios Retrospectivos
9.
J Clin Med ; 10(9)2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33946877

RESUMEN

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare cholestatic liver disease triggered by long-term intensive care treatment. The aim of this study was to evaluate the frequency and characteristics of gastrointestinal bleeding in SC-CIP. Patients with diagnosed SC-CIP were retrospectively identified and compared to a control group of patients with cardiac surgery and intensive care treatment but without the development of SC-CIP. Fifty-three patients with SC-CIP and 19 controls were included in the study. The frequency of gastrointestinal bleeding was 30% in SC-CIP (16 patients) and 5% in the control group (1 patient) (p = 0.03). Bleeding occured in the mean 13 months after admission to an intensive care unit in SC-CIP, three patients (19%) suffered bleeding during intensive care treatment. Three SC-CIP patients (19%) had cirrhosis at the time of bleeding, five (31%) had splenomegaly, and four (25%) received oral anticoagulation. In SC-CIP, 13 bleedings were identified in the upper gastrointestinal tract, two in the lower, and one remained unknown. The most common reasons for bleeding were gastroduodenal ulcers. In total, 80% of patients needed blood units, and one death due to bleeding occurred in SC-CIP. In conclusion, gastrointestinal bleeding is a frequent complication in patients with SC-CIP. Whether the liver disease itself or cofactors cause the susceptibility for bleeding remains unclear.

10.
Nutrients ; 13(3)2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33801133

RESUMEN

The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.


Asunto(s)
Colestasis/microbiología , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/metabolismo , Hígado/metabolismo , Animales , Traslocación Bacteriana , Ácidos y Sales Biliares , Colangitis Esclerosante/tratamiento farmacológico , Colangitis Esclerosante/microbiología , Colestasis/patología , Disbiosis , Humanos , Inflamación , Cirrosis Hepática Biliar/microbiología , Hepatopatías , Estrés Oxidativo
11.
Inflamm Bowel Dis ; 27(11): 1773-1783, 2021 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33386735

RESUMEN

BACKGROUND: Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. METHODS: This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. RESULTS: We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. CONCLUSION: The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Hemorragia , Enfermedades Inflamatorias del Intestino , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología
13.
Nutrients ; 12(9)2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32906634

RESUMEN

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut-liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut-liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.


Asunto(s)
Colangitis Esclerosante/microbiología , Enfermedad Crítica , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Hígado/fisiología , Proteínas de Fase Aguda , Adulto , Anciano , Bacterias/clasificación , Ácidos y Sales Biliares , Proteínas Portadoras , Estudios de Casos y Controles , Colangitis Esclerosante/complicaciones , Cuidados Críticos , Femenino , Tracto Gastrointestinal/fisiología , Haptoglobinas , Humanos , Complejo de Antígeno L1 de Leucocito , Cirrosis Hepática/complicaciones , Masculino , Glicoproteínas de Membrana , Persona de Mediana Edad , Precursores de Proteínas
14.
Sci Rep ; 10(1): 2723, 2020 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-32066847

RESUMEN

Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (-18.8 ng/mg; 95%CI: -50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (-46.3 ng/mg; 95%CI: -71.4; -21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.


Asunto(s)
Antiulcerosos/efectos adversos , Disbiosis/prevención & control , Reflujo Gastroesofágico/terapia , Úlcera Péptica/terapia , Prebióticos/administración & dosificación , Probióticos/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Anciano , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Antiulcerosos/administración & dosificación , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/metabolismo , Bacillus/clasificación , Bacillus/aislamiento & purificación , Clostridiales/clasificación , Clostridiales/aislamiento & purificación , Disbiosis/inducido químicamente , Disbiosis/fisiopatología , Esomeprazol/administración & dosificación , Esomeprazol/efectos adversos , Femenino , Reflujo Gastroesofágico/microbiología , Reflujo Gastroesofágico/fisiopatología , Microbioma Gastrointestinal/fisiología , Regulación de la Expresión Génica , Haptoglobinas/genética , Haptoglobinas/metabolismo , Humanos , Lactobacillus/clasificación , Lactobacillus/aislamiento & purificación , Lactococcus/clasificación , Lactococcus/aislamiento & purificación , Complejo de Antígeno L1 de Leucocito/genética , Complejo de Antígeno L1 de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Pantoprazol/administración & dosificación , Pantoprazol/efectos adversos , Úlcera Péptica/microbiología , Úlcera Péptica/fisiopatología , Proyectos Piloto , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Inhibidores de la Bomba de Protones/administración & dosificación , Calidad de Vida
15.
Liver Int ; 40(4): 866-877, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31943691

RESUMEN

BACKGROUND & AIMS: Compositional changes of the faecal microbiome in cirrhosis are well described and have been associated with complications and prognosis. However, it is less well known, which disease or treatment-related factors affect microbiome composition most distinctively. METHODS: 16S rDNA sequencing data of 88 cirrhotic outpatients were investigated. Factors influencing microbiome composition were analysed by univariate and multivariate redundancy analysis. The association of the identified factors with changes in diversity and taxonomic composition was studied in depth using analysis of composition of microbiome, LDA-effect size and least absolute shrinkage and selection operator regularized regression. RESULTS: Disease severity and aetiology, proton pump inhibitor (PPI) use, nutritional status, age and C-reactive protein are significant explanatory variables for faecal microbiome composition in liver cirrhosis. Despite some taxonomic overlaps especially between disease severity and PPI use, we could show that the effects of disease severity, aetiology, PPI use and age are independent factors influencing microbiome composition also in subgroup analyses. CONCLUSION: Our cross sectional system biology study identifies disease severity, aetiology, PPI use and age as independent factors that influence microbiome composition in liver cirrhosis. In chronic diseases with high morbidity, such as liver cirrhosis, precise patient metadata documentation is of utmost importance in microbiome analysis. Further studies with a higher sample size are necessary to validate this finding. TRIAL REGISTRATION NUMBER: NCT01607528.


Asunto(s)
Microbiota , Inhibidores de la Bomba de Protones , Estudios Transversales , Humanos , Cirrosis Hepática , Inhibidores de la Bomba de Protones/uso terapéutico , Índice de Severidad de la Enfermedad
17.
Eur J Nutr ; 59(7): 2969-2983, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31729622

RESUMEN

PURPOSE: Diabesity, the combination of obesity and type 2 diabetes, is an ever-growing global health burden. Diabesity-associated dysbiosis of the intestinal microbiome has gained attention as a potential driver of disease and, therefore, a possible therapeutic target by means of pro- or prebiotic supplementation. This study tested the effects of a multispecies synbiotic (i.e. a combination of probiotics and prebiotics) on glucose metabolism, gut microbiota, gut permeability, neutrophil function and quality of life in treatment-experienced diabesity patients. METHODS: A randomized, double-blind, placebo-controlled pilot study with 26 diabesity patients was conducted in which patients received a daily dose of a multispecies probiotic and a prebiotic (or a placebo) for 6 months. RESULTS: There were no changes in glucose metabolism or mixed meal tolerance test responses throughout the study. The analysis of secondary outcomes revealed beneficial effects on hip circumference [- 1 (95% CI - 4; 3) vs +3 (- 1; 8) cm, synbiotics vs. placebo, respectively, p = 0.04], serum zonulin [- 0.04 (- 0.2; 0.1) vs +0.3 (- 0.05; 0.6) ng/ml, p = 0.004)] and the physical role item of the SF36 quality of life assessment [+ 5.4 (- 1.7; 12.5) vs - 5.0 (- 10.1; 0.2) points, p = 0.02] after 3 months of intervention, and lipoprotein (a) [- 2.1 (- 5.7; 1.6) vs +3.4 (- 0.9; 7.9) mg/dl, p = 0.02] after 6 months. There were no significant differences in alpha or beta diversity of the microbiome between groups or time points. CONCLUSIONS: Glucose metabolism as the primary outcome was unchanged during the intervention with a multispecies synbiotic in patients with diabesity. Nevertheless, synbiotics improved some symptoms and biomarkers of type 2 diabetes and aspects of quality of life suggesting a potential role as adjuvant tool in the management of diabesity.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Probióticos , Simbióticos , Biomarcadores , Método Doble Ciego , Glucosa , Humanos , Lípidos , Permeabilidad , Proyectos Piloto , Calidad de Vida
18.
Z Gastroenterol ; 57(11): 1304-1308, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31739376

RESUMEN

Selective internal radiation therapy (SIRT) is a therapeutic option for primary and metastatic liver tumors. Microspheres containing Yttrium 90, a beta-emitting radionuclide, are administered into the hepatic artery allowing selective internal radiation of a liver tumor. SIRT-related complications may appear due to migration of the radiation microspheres to organs distant from the tumor site. In order to prevent these complications, unintended non target embolization of Yttrium microspheres has to be avoided. However, data from external-beam radiation therapy (EBRT) suggests that the stomach/small bowel may actually be less radiosensitive than the liver. Gastric ulcers, a well-known SIRT-related complication, may therefore not only be caused by local radiation but also by unusual accumulation of microspheres in the submucosa and small vessel damage. We herein report a more than two- year-long persisting, highly symptomatic, non-neoplastic ulceration of the gastric antrum leading to pyloric stenosis caused by SIRT therapy with Yttrium 90 microspheres for the treatment of intrahepatic cholangiocellular carcinoma. The chronic courses of the ulcer disease together with the specific histological features highlight the pivotal role of radiation-induced small vessel damage in SIRT-induced adverse events.


Asunto(s)
Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/radioterapia , Colangiocarcinoma/patología , Colangiocarcinoma/radioterapia , Traumatismos por Radiación/diagnóstico , Úlcera Gástrica/etiología , Radioisótopos de Itrio/efectos adversos , Conductos Biliares Intrahepáticos , Femenino , Arteria Hepática , Humanos , Microesferas , Persona de Mediana Edad , Úlcera Gástrica/diagnóstico , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéutico
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