P125 Could gut microbiota metagenomic analysis improve diagnosis in paediatric Inflammatory Bowel Disease population?

Abstract Background Gut microbiota plays an important role in maintaining intestinal homeostasis. Recent studies postulate that dysbiosis may be involved in the pathogenesis of Inflammatory Bowel Disease (IBD). The aim of the study was to characterize the metagenomic biodiversity of the gut microbiota in Paediatric Inflammatory Bowel Disease patients (PIBD) and whether microbiome data could be used as diagnostic tool. Methods A prospective, longitudinal observational pilot clinical trial with consecutive inclusion of PIBD patients matched with healthy controls by age and sex was performed. A total of 36 children were planned to be included: 12 Crohn’s Disease (CD), 12 Ulcerative Colitis (UC) and 12 healthy controls (HC). Demographic, clinical and analytical data were recorded and stool and saliva samples were collected at onset, 3 and 6 months for DNA sequencing and bioinformatics analysis. Results Twenty-three patients (12CD, 11UC) and 9 HC were included (at the time of data analysis). Fifty-six percent were male; mean age: 11.7 years (IQR: 8–15). CD patients at onset had a mean Paediatric Crohn’s Disease Activity Index (PCDAI) of 22.5 (IQR: 10–55), a mean Faecal Calprotectin (FC) of 2384 mg/kg (IQR: 159–6000) and 83% of them had inflammatory markers elevation (Erythrocyte Sedimentation Rate (ESR) and/or C-reactive protein (CRP)). Patients with UC presented a mean Paediatric Ulcerative Colitis Activity Index (PUCAI) of 43.6 (IQR: 10–80) at onset, mean CF of 3381 mg/kg and 18% presented an increase of inflammatory markers (ESR and/or CRP). To date, Next Generation Sequencing (NGS) metagenomic study (saliva and stools) has been performed from 15 subjects (9 CD, 2 UC and 4 HC) at onset and 9 subjects (7 CD and 2 UC) at 3 months. A differential microbiota pattern was observed in both, saliva and stools, for CD at onset and at 3 months. In the stools, three differential taxa were found at onset of the disease and at 3 months and in saliva, another three differential taxa were observed compared to HC. In UC, 6 differential taxa (> 3 % diff. HC-UC, p-value=0) were selected in stools and 7 in saliva at onset compared to HC. Globally, a higher microbial biodiversity was observed for HC compared to CD at onset, but it was not statistically significant. Conclusion Provisional results showed a possible differential signature in both saliva and stools of patients with paediatric CD. These results must be validated with all the samples in process, and probably using larger paediatric cohorts before the development of these techniques as a diagnostic tool in the clinical practice.

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Calibrated automated thrombin generation in paediatric patients with inflammatory bowel disease

Hämostaseologie ◽

10.1055/s-0037-1621491 ◽

2009 ◽

Vol 29 (S 01) ◽

pp. S90-S93 ◽

Cited By ~ 4

Author(s):

H. Bernhard ◽

A. Deutschmann ◽

B. Leschnik ◽

M. Novak ◽

A. Hauer ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Disease Activity ◽

Bowel Disease ◽

Thrombin Generation ◽

Activity Index ◽

Disease Activity Index ◽

Healthy Controls ◽

Inflammatory Bowel

SummaryIn adults, inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolic complications. The pathogenesis of IBD is not really clear and a high thrombin activity might contribute to disease progression. We wanted to see whether children with IBD have a higher thrombin generation (TG). Patients, material, methods: Plasma samples were collected of 20 patients with IBD and of 60 healthy controls (age range from 10 to 19). TG was measured by means of Calibrated automated thrombography (CAT). The disease activity was estimated, using the Pediatric Crohn‘s Disease Activity Index (PCDAI) for Crohn‘s disease and the Pediatric Ulcerative Colitis Disease Activity Index (PUCAI) for Ulcerative Colitis. In addition, we investigated F1+F2, TAT, TFPI and fibrinogen. Results: There was a significant increase of endogenous thrombin potential (ETP), lag time and time to peak in patients with IBD, while peak showed no difference to healthy controls. ETP and F1+F2 in children with IBD also showed a significant correlation with PCDAI (PUCAI) and fibrinogen. Conclusion: IBD in children is associated with high TG, but this seems to be caused mainly by the inflammatory process and not by any individual disposition.

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Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

Zeitschrift für Gastroenterologie ◽

10.1055/a-0605-4080 ◽

2018 ◽

Vol 56 (10) ◽

pp. 1267-1275 ◽

Cited By ~ 1

Author(s):

Angelika Hüppe ◽

Jana Langbrandtner ◽

Winfried Häuser ◽

Heiner Raspe ◽

Bernd Bokemeyer

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Inflammatory Bowel ◽

Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

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The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease

BMC Gastroenterology ◽

10.1186/s12876-020-01435-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Carlijn R. Lamers ◽

Nicole M. de Roos ◽

Ben J. M. Witteman

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Statistical Significance ◽

Inflammatory Bowel ◽

Anti Inflammatory

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

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Sleep Impairment and Psychological Distress among Patients with Inflammatory Bowel Disease—beyond the Obvious

Journal of Clinical Medicine ◽

10.3390/jcm9072304 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2304

Author(s):

Georgiana-Emmanuela Gîlc-Blanariu ◽

Gabriela Ștefnescu ◽

Anca Victorița Trifan ◽

Mihaela Moscalu ◽

Mihail-Gabriel Dimofte ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Psychological Distress ◽

Sleep Quality ◽

Bowel Disease ◽

Anxiety And Depression ◽

Healthy Controls ◽

Sleep Impairment ◽

Inflammatory Bowel

Background: A healthy sleep–wake cycle is fundamental for regulating immune function. Sleepiness and fatigue are often manifestations of chronic inflammatory disorders, such as inflammatory bowel disease (IBD), potentially influencing the course of the disease. Our aim was to characterize sleep impairment in patients with IBD and to identify potential associated factors. Methods: We conducted a single-center prospective case control study including IBD patients and healthy controls. We evaluated clinical and biochemical parameters, sleep impairment through Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression through Hospital Anxiety and Depression Scale (HADS) questionnaires. Results: In total, 110 patients with IBD and 66 healthy controls were included. Patients with IBD had a significantly altered sleep quality compared to the control group (p < 0.001), with sleep impairment also occurring for patients in remission (median PSQI = 7), but without significant differences between ulcerative colitis and Crohn’s disease. However, PSQI was correlated with disease activity scores only for ulcerative colitis and not for Crohn’s disease. Among patients with increased PSQI, only 30.19% used sleep medication. Sleep impairment was significantly correlated with altered psychological status (p < 0.01) and the presence of extraintestinal manifestations (p = 0.0172). Conclusions: Sleep impairment is frequent among patients with IBD, is associated with psychological distress and several disease-related parameters and should be routinely evaluated, at least in several IBD patient subgroups, to improve disease management.

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Features of very early-onset inflammatory bowel disease: the experience of the Federal Pediatric Center

Voprosy detskoj dietologii ◽

10.20953/1727-5784-2021-3-5-13 ◽

2021 ◽

Vol 19 (3) ◽

pp. 5-13

Author(s):

P.V. Shumilov ◽

◽

A.E. Shchigoleva ◽

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Primary Immunodeficiency ◽

Bowel Disease ◽

Early Onset ◽

Activity Index ◽

Response To Therapy ◽

Inflammatory Bowel

Objective. To clarify the incidence of monogenic IBD-like diseases and the features of clinical course and response to therapy of major types of inflammatory bowel diseases (IBD) among children under the age of 6 with manifestation of the disease. Patients and methods. The study included 135 children under the age of 6 with manifestation of IBD; in the comparison group, there were 128 children after the age of 6 with manifestation of IBD (97 children with ulcerative colitis (UC) and 31 children with Crohn’s disease (CD)) who were observed for at least 1 year. All children underwent a standard examination, including calprotectin and antineutrophil antibodies testing, determination of activity by the Pediatric Ulcerative Colitis Activity Index (PUCAI) or the Pediatric Crohn’s Disease Activity Index (PCDAI), depending on the nosology. Children with the onset of IBD under 6 years of age underwent a genetic testing using Primary Immunodeficiency Panel by next-generation sequencing. All children were analyzed for efficacy of therapy during catamnestic observation. Results. It was revealed that in the study group the incidence of monogenic IBD-like diseases was 6.7%, of UC – 71.1%, of CD – 22.2%. Major types of IBD with very early onset differed little in their clinical, endoscopic and laboratory features from the forms with manifestation at an older age. In most cases, both CD (57%) and UC (71%) were characterized by low activity. Very earlyonset CD was characterized by isolated localization of the colon (53%, p = 0.037) and a non-stenotic and non-penetrating behaviour of the disease (60% of cases). The leading clinical symptoms were diarrhea (67%) and blood in the stool (63%, p = 0.04). Very early-onset UC was characterized by total lesion of the colon (84%, p = 0.001) and the development of anemia (48%, p = 0.01). Among children with very early-onset UC, the percentage of glucocorticosteroid-dependence and glucocorticosteroid-resistance was high, but anti-TNFα therapy was prescribed late. Conclusion. It is advisable to observe children with very early-onset IBD in federal multidisciplinary clinics, where there is experience in managing patients with this pathology. Key words: inflammatory bowel disease, very early onset, Crohn’s disease, ulcerative colitis, primary immunodeficiency, treatment, children

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Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease

Diagnostics ◽

10.3390/diagnostics11061090 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1090

Author(s):

Flavia Maria Pavel ◽

Cosmin Mihai Vesa ◽

Gina Gheorghe ◽

Camelia C. Diaconu ◽

Manuela Stoicescu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Gut Microbiome ◽

Activity Index ◽

Remission Rate ◽

Fecal Transplantation ◽

Inflammatory Bowel

Two different conditions are included in inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or “dysbiosis”. Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.

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Detection of anti-colon antibodies in inflammatory bowel disease using human cultured colonic cells

Gut ◽

10.1136/gut.44.2.196 ◽

1999 ◽

Vol 44 (2) ◽

pp. 196-202 ◽

Cited By ~ 11

Author(s):

J C W Lee ◽

A M Cevallos ◽

A Naeem ◽

J E Lennard-Jones ◽

M J G Farthing

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Immune Response ◽

Crohn’S Disease ◽

Antibody Response ◽

Cell Lines ◽

Bowel Disease ◽

Gastrointestinal Disorders ◽

Healthy Controls ◽

Inflammatory Bowel

BackgroundInvestigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available.AimsTo examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen.SubjectsPatients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied.MethodsComparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis.ResultsSera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn’s disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (p<0.05). The immune response was not associated with one predominant antigen.ConclusionsFixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn’s disease.

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Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2014.1323568 ◽

2014 ◽

Vol 132 (3) ◽

pp. 140-146 ◽

Cited By ~ 13

Author(s):

Rodrigo Andrade Alves ◽

Sender Jankiel Miszputen ◽

Maria Stella Figueiredo

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Iron Deficiency ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Deficiency Anemia ◽

Inflammatory Bowel

CONTEXT AND OBJECTIVES:Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables.DESIGN AND SETTING:Cross-sectional at a federal university.METHODS:44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated.RESULTS:Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index.CONCLUSIONS:Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index.

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Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2004.111 ◽

2004 ◽

Vol 42 (6) ◽

Cited By ~ 6

Author(s):

Anne Schmedes ◽

Jens Nederby Nielsen ◽

Henrik Hey ◽

Ivan Brandslund

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

High Pressure ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Hydrogen Sulphide ◽

Bowel Disease ◽

Whole Blood ◽

Activity Index ◽

Inflammatory Bowel

AbstractBackground: S-adenosylmethionine is a methyl donor in many cellular reactions including detoxification of constantly produced hydrogen sulphide in the colon. A reduced capacity to detoxify hydrogen sulphide may be implicated in the pathogenesis of inflammatory bowel disease. S-adenosylmethionine could be low if this assumption is correct. We compared S-adenosylmethionine concentrations in whole blood in patients with severe and moderate inflammatory bowel disease with healthy reference persons. Methods: S-adenosylmethionine concentrations in whole blood were measured using high-pressure liquid chromatography. Patients with Crohn's disease (n=21), ulcerative colitis (n=7) and healthy age-matched reference persons (or controls) (n=17) were studied. Results: S-adenosylmethionine concentrations were significantly decreased in patients with severe inflammatory bowel disease (mean 1.10 mg/l) as compared to patients with moderate Crohn's disease and ulcerative colitis (mean 1.83 mg/l) and reference persons (mean 1.84 mg/l). Statistically significant inverse correlations were found between S-adenosylmethionine concentration and activity index (p<0.01 and R

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Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

Current Clinical Pharmacology ◽

10.2174/1574884715666200312100237 ◽

2020 ◽

Vol 15 (3) ◽

pp. 216-233 ◽

Cited By ~ 1

Author(s):

Maliha Naseer ◽

Shiva Poola ◽

Syed Ali ◽

Sami Samiullah ◽

Veysel Tahan

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Bowel Disease ◽

Relapse Prevention ◽

Remission Induction ◽

Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

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