Serum concentrations of fibrosis markers in children with inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: The aim of the study was to assess the usefulness of serum concentrations of YKL-40/ CHI3L1 (a 40-kilodalton glycoprotein also referred to as chitinase 3 like- 1 - CHI3L1) and PIIINP (N-terminal propeptide of type III procollagen), markers of fibrosis, in the monitoring of inflammatory processes and fibrosis in children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: In 60 patients (41 with Crohn's disease (CD), 19 with ulcerative colitis (UC)) concentrations of investigated parameters were measured at baseline (day 0), after 3 and after 6-8 weeks of pharmacological treatment. RESULTS: PIIINP concentrations were significantly higher in CD patients compared to UC (baseline results: median concentrations 1013.73 vs 78.30 ng/mL; P = 0.06 for the Kruskall-Wallis test; results at 6-8 weeks: 1076.48 vs 53.10 ng/mL, P = 0.01). Fibrosis was clearly present in patients with CD and its severity increased (reflected by both YKL-40/ CHI3L1 and PIIINP concentrations) in 6-8 weeks of follow up, regardless of the treatment used during that time. In patients with UC the levels of YKL-40/CHI3L1 and PIIINP were lower at baseline and further decreased after 6-8 weeks (median concentrations were respectively: 39.5 ng/mL vs 24.7 ng/mL and 78.3 ng/mL vs 53.1 ng/mL). CONCLUSION: Fibrosis was more severe in CD than in UC patients. The marker that more accurately reflected these differences was PIIINP.

[Retrospective analysis of epidemiological and clinical aspects of acute pancreatitis in children]. / Retrospektywna analiza epidemiologiczna i kliniczna ostrego zapalenia trzustki u dzieci.

UNLABELLED: Acute pancreatitis (AP) is becoming more frequent cause of hospitalization in children. There are no guidelines concerning optimal medical treatment in this condition, up to know. The aim of the study was the epidemiological and clinical assessment of AP in pediatric population. The evaluation of influence of administered pharmacotherapy on symptoms remission and the time of laboratory tests normalization. MATERIAL AND METHODS: There were 54 patients with AP, in the age of 3, 5-18 years, admitted to our hospital between 1994-2011. The investigation was led on the basis of retrospective analysis of medical data. RESULTS: 41 (75%) patients were admitted with the first episode of AP. The oedematous pancreatitis was confirmed in 49 patients (91%) and necrotizing pancreatitis in 5 cases (9%). The cause of the condition was determined in 44 cases. The most common clinical symptoms were epigastric pain (94%) and vomiting (43%). CONCLUSIONS: There was no statistically significant difference in the time of obtaining normal range of serum and urine amylase activity and relief of symptoms according to administered pharmacotherapy and nutritional therapy

Liver fibrosis assessment in pediatric population - can ultrasound elastography be an alternative method to liver biopsy? A systematic review.

Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.

Endogenous Opioids in Crohn's Disease.

Caring for patients with Crohn's disease (CD) is a serious challenge in modern medicine. The increasing incidence of CD among adolescents and the severe course of the disease create the need for new methods of diagnosis and therapy. Endogenous opioids are a group of low molecular weight chemical compounds with analgesic and anti-inflammatory properties. Endorphins, enkephalins, and dynorphins may have potentially beneficial effects on the course of CD. Previous research data on this topic are inconsistent. Some authors have reported an increase in the concentration of leukocytes during the course of inflammatory bowel disease (IBD) while others have described a downward trend, explained by DPP-IV enzyme activity. Even fewer data are available on plasma endo-opioid level. There is also a lack of comprehensive studies that have assessed the endo-opioid system in patients with IBD. Therefore, the objective of this study was to measure the serum concentrations of human ß-endorphin, human proenkephalin (A), and human big dynorphin in CD patients in the acute phase of the disease, during hospital treatment, and in the remission state. All determinations were performed using ELISA kits. The results of our study showed that the concentrations of all the tested endo-opioids, especially ß-endorphin and proenkephalin (A), were reduced in adolescents with CD compared to those in the healthy control group, during the acute phase of the disease, and in the remission state. Modulation of the endogenous opioid system and the use of selective nonnarcotic agonists of opioid receptors seems to be promising goals in the future treatment of CD.

Prevention and Health Benefits of Prebiotics, Probiotics and Postbiotics in Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children, comprising 75-85% of cases. Aggressive treatment of leukemias includes chemotherapy and antibiotics that often disrupt the host microbiota. Additionally, the gut microbiota may play a role in the development and progression of acute leukemia. Prebiotics, probiotics, and postbiotics are considered beneficial to health. The role of prebiotics in the treatment and development of leukemia is not well understood, but inulin can be potentially used in the treatment of leukemia. Some probiotic bacteria such as Lactobacillus shows anticancer activity in in vitro studies. Additionally, Bifidobacterium spp., as a consequence of the inhibition of growth factor signaling and mitochondrial-mediated apoptosis, decrease the proliferation of cancer cells. Many bacterial metabolites have promising anticancer potential. The available research results are promising. However, more research is needed in humans, especially in the child population, to fully understand the relationship between the gut microbiota and acute leukemia.

Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease.

BACKGROUND AND AIMS: The commensal microbiota of the gastrointestinal tract plays an important role in the pathogenesis of inflammatory bowel disease. We examined the horizontal structure of the fecal microbiota in the colon in adolescents with Crohn disease or ulcerative colitis and a control group. PATIENTS AND METHODS: Fecal samples were collected in 3 fractions from patients with Crohn disease (n = 22), ulcerative colitis (n = 12), and controls (n = 24) during preparation for colonoscopy. Additionally, biopsies from colon tissue were taken. Samples were examined using a culture technique and a fluorescent in situ hybridization method. The mucin degradation assay was carried out. RESULTS: Quantitative composition of the microbiota was different in the consecutive 3 fecal fractions and in the colon tissue of the study groups, but in patients from the control group, the composition of microbiota in the consecutive fractions was similar. Statistical analyses showed that the total distribution of the studied bacterial taxons in the contents in all 3 fecal fractions and in the colon tissue in the given disease group, and in the control group was characteristic for the studied patient group. Differences in species distribution among the cohorts studied were highly significant (P < 0.0001). Moreover, it was shown that in the fecal fraction I and in the colon tissue samples, there is no significant difference for any of the analyzed bacterial groups, using the culture methods or fluorescent in situ hybridization, but significant results were demonstrated in the II and III fractions for specific bacterial groups. The bacterial flora attached to the mucus layer in the UC group had significantly more degraded mucus in comparison with the control group (P = 0.045). CONCLUSIONS: Distribution of the microbiota in the colon is layered, which can be called horizontal distribution of the fecal flora. Only in the ulcerative colitis group, the bacterial flora attached to the mucous layer exerts action on the mucin.

Prebiotics, Probiotics, and Postbiotics in the Prevention and Treatment of Anemia.

Iron deficiency anemia (IDA) is very common and affects approximately 1/3 of the world's human population. There are strong research data that some probiotics, such as Lactobacillus acidophilus and Bifidobacterium longum improve iron absorption and influence the course of anemia. Furthermore, prebiotics, including galactooligosaccharides (GOS) and fructooligosaccharides (FOS), increase iron bioavailability and decrease its destructive effect on the intestinal microbiota. In addition, multiple postbiotics, which are probiotic metabolites, including vitamins, short-chain fatty acids (SCFA), and tryptophan, are involved in the regulation of intestinal absorption and may influence iron status in humans. This review presents the actual data from research studies on the influence of probiotics, prebiotics, and postbiotics on the prevention and therapy of IDA and the latest findings regarding their mechanisms of action. A comparison of the latest research data and theories regarding the role of pre-, post-, and probiotics and the mechanism of their action in anemias is also presented and discussed.

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients.

Background: In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms. Methods: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used. Results: We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups. Conclusion: Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.

Serum concentrations of VEGF and TGF-ß1 during exclusive enteral nutrition in IBD.

BACKGROUND AND AIM: Exclusive enteral nutrition (EEN) is an effective method of treatment in achieving remission in inflammatory bowel disease (IBD); however, its mechanism of action is still poorly understood. The objective of our study was to assess the influence of EEN on serum vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-ß1) in children and adolescents with IBD. PATIENTS AND METHODS: Thirty-nine children and adolescents with IBD (24 with Crohn disease [CD] and 15 with ulcerative colitis [UC]) and 25 healthy controls were enrolled in the study. VEGF and TGF-ß1 were assessed at the baseline and after 2 and 4 weeks of EEN in CD and UC groups and once in controls using enzyme-linked immunosorbent assay immunoassays. RESULTS: At the baseline, we found increased serum VEGF in the CD versus UC group and controls (P < 0.05) and serum TGF-ß1 in the UC versus CD group and controls (P < 0.05). During EEN, VEGF decreased in the UC and CD groups, whereas TGF-ß1 increased in the CD group and decreased in the UC group. The CD group achieved disease remission faster than the UC group, and the weight gain of patients with CD during EEN was higher compared with patients with UC. Additionally, TGF-ß1 concentration correlated with protein and energies daily intake in the CD group (R = 0.95; P < 0.05). CONCLUSIONS: Different effectiveness of EEN in achieving remission in CD and UC may result from a modification of growth factor production. EEN stimulated TGF-ß1 production in CD but not in UC, which possibly resulted in higher effectiveness of EEN in this group of patients.

Peptides from adipose tissue in monitoring energy balance in infants.

BACKGROUND/AIM: Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. METHODS: Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. RESULTS: Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake. CONCLUSIONS: Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Plasma elafin, cathelicidin, and α-defensins are increased in paediatric inflammatory Crohn's disease and reflect disease location.

INTRODUCTION: The aim of our study was to assess antimicrobial peptides in children with Crohn's disease (CD). METHODS: Plasma elafin, cathelicidin, and α- and ß-defensins were assessed in 35 children with CD using immunoassays. Phenotype and location of CD were assessed based on the results of endoscopic and radiological studies. RESULTS: We found increased elafin, cathelicidin, and α-defensins in children with inflammatory phenotype as compared to stricturing and penetrating phenotypes of CD. Additionally, we found increased elafin and cathelicidin in colonic location and α-defensins in ileal CD locations. CONCLUSIONS: Assessing antimicrobial peptides may be helpful in estimating of phenotype and location of CD lesions.

Effect of Selected Factors on the Serum 25(OH)D Concentration in Women Treated for Breast Cancer.

Maintaining an optimal vitamin D concentration reduces the risk of recurrence and extends survival time in patients after breast cancer treatment. Data on vitamin D deficiency among Polish women after breast cancer therapy are limited. Thus, the aim of the study was the analysis of vitamin D status in post-mastectomy patients, considering such factors as seasons, social habits, vitamin D supplementation and its measurements. The study involved 94 women after breast cancer treatment. Serum vitamin D concentration was measured, and a questionnaire, gathering demographic and clinical data regarding cancer, diet, exposure to sun radiation, and knowledge of recommendations on vitamin D supplementation, was delivered twice, in both winter and in summer. The control group consisted of 94 age-matched women with no oncological history. In women after breast cancer treatment, 25-hydroxyvitamin D (25(OH)D) deficiency was much more frequent than in the general population. Only about half of the patients supplemented vitamin D at the beginning of the study. After the first test and the issuing of recommendations on vitamin D supplementation, the percentage of vitamin D supplemented patients increased by about 30% in study groups. The average dose of supplement also increased. None of the women that were not supplementing vitamin D and were tested again in winter had optimal 25(OH)D concentration. It was concluded that vitamin deficiency is common in women treated for breast cancer. Medical advising about vitamin D supplementation and monitoring of 25(OH)D concentration should be improved.

Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD.

The increasing incidence of inflammatory bowel diseases (IBD) and the increasing severity of the course of these diseases create the need for developing new methods of therapy. The gut microbiome is extensively studied as a factor influencing the development and course of IBD. The composition of intestinal microbiota can be relatively easily modified by diet (i.e., prebiotics, mainly dietary fibers) and bacterial supplementation using beneficial bacteria strains called probiotics. Additionally, the effects of the improved microbiome could be enhanced or gained by using paraprobiotics (non-viable, inactivated bacteria or their components) and/or postbiotics (products of bacterial metabolism or equal synthetic products that beneficially modulate immunological response and inflammation). This study summarizes the recent works on prebiotics, probiotics, synbiotics (products merging pre- and probiotics), paraprobiotics and postbiotics in IBD.

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose-Lipid Metabolism.

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6-17.7) and 10 healthy (aged 11.4-16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.

[Influence of enteral nutrition therapy on serum angiogenic growth factors concentrations in children]. / Wplyw zywienia enteralnego na stezenia czynników naczyniowzrostowych w surowicy u dzieci.

INTRODUCTION: Effectiveness of enteral nutrition therapy is not only connected with improvement of the nutritional status of the patient, but also with its strong anti-inflammatory activity. Angiogenic growth factors play an important role in the early stage of inflammation. Vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) stimulate the angiogenesis and healing processes. The objective of our study was to assess the influence of the enteral nutrition therapy on the vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) concentrations in serum in children with different diseases of gastro-intestinal tract, in which enteral nutrition therapy is effective method of treatment. MATERIAL AND METHODS: Sixty two children (29 boys, 33 girls, mean age: 12.5 yrs, range: 6-18 yrs) and 25 healthy controls were included into the study. The Crohn's disease group (CD) consisted of 25 patients, ulcerative colitis group (UC)-18 patients, acute pancreatitis (AP) group-12 patients and severe malnutrition (N) group-7 patients. Serum VEGF and TGF-beta 1 concentrations were assessed at baseline, before starting and after 2 and 4 weeks of enteral nutrition therapy using ELISA immunoassays (R and D Systems, USA). RESULTS: Before starting enteral nutrition, we found increased VEGF concentration in CD group (Me = 600 pg/ml) compared to UC group (266.9 pg/ml), AP group (552.6 pg/ml), N group (238.5 pg/ml) and controls (172 pg/ml) (p < 0.05). We found decrease of VEGF concentrations during enteral nutrition in CD, UC and N group and increase in AP at the beginning, followed by decrease to the initial values. Assessing TGF-beta 1, we found its concentration increased before starting enteral nutrition in UC group (37.5 ng/ml) compared to CD group (29.7 ng/ ml) and controls (24.8 ng/ml) (p < 0.05). During enteral nutrition we observed decrease of TGF-beta 1 concentration in UC group and increase in CD group (32,7 ng/ml) and AP group (26,6 ng/ml) (p < 0.05) The best improvement of nutritional status was observed in CD patients compared to N and AP patients. CONCLUSIONS: Differentiation of serum VEGF and TGF-beta 1 concentrations, what was observed in various gastro-intestinal diseases, reflects different mechanisms of enteral nutrition therapy acting on the inflammatory process. The most efficient therapeutic effect was seen in CD, where stimulation of TGF-beta 1 production was observed.

Infliximab Therapy Could Decrease the Risk of the Development of Thyroid Disorders in Pediatric Patients With Crohn's Disease.

Autoimmune diseases, including autoimmune thyroid diseases (AITDs), may be associated with Crohn's disease (CD). Taking into consideration the role of tumor necrosis factor alpha (TNF-alpha) in the immune-mediated inflammation that underlies both diseases, we evaluated an ultrasound of thyroid gland in pediatric CD patients, naïve, and treated with infliximab (IFX), an anti-TNF-alpha antibody, to assess the risk for AITD and evaluated the usefulness of ultrasonography to diagnose AITD in patients with CD. Sixty-one patients with CD were enrolled in the study, including 36 patients (mean age 14.5 ± 3.5 years) treated with IFX (IFX group) for a mean of 13.9 ± 16.6 months and 25 patients (mean age 14.7 ± 2.3 years) who never received anti-TNF-alpha therapy (control group). An ultrasound examination of the thyroid gland was performed; thyroid function tests and thyroid antibodies were assessed. We found 10-times higher prevalence of decreased thyroid echogenicity in CD and IFX-naive patients compared to IFX-treated group [a significant reduction in thyroid echogenicity in 1/36 (2.8%) patients receiving IFX compared to 7/25 (28%) patients naive to biologic therapy]. The latter showed significantly lower thyroid-stimulating hormone (TSH) levels (p = 0.034) and higher levels of thyroid antibodies (p = 0.042) in comparison to control. Our data suggest the protective role of IFX therapy in the development of thyroid disorders and indicate the usefulness of thyroid ultrasound to identify the risk of probable AITD in pediatric patients with CD.

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Dependence of Colonization of the Large Intestine by Candida on the Treatment of Crohn's Disease.

The aim of this study was to determine if there are quantitative differences in Candida fungi between pediatric patients with Crohn's disease (before and after exclusive enteral nutrition (EEN), and the biologic therapy with anti-tumor necrosis factor alpha - (IFX)), and healthy controls. DNA was isolated from fecal samples and PCR was used to determine the number of fungal cells. Both therapeutic interventions resulted in a statistically significant decrease in Pediatric Crohn's Disease Activity Index. The numbers of Candida decreased during both therapeutic intervention but the difference was statistically significant for the IFX intervention only (p = 0.045). Moreover, fungi population in both study groups declined during intervention when compared to the control group but the difference was significant before treatment only in the IFX group (p = 0.013). The total distribution of Candida with both IFX and EEN as well as in the control group differed significantly (p = 0.01) before treatment only. No correlation between the numbers of Candida and disease activity as well as the following biochemical parameters: serum iron concentration, protein or glucose level were found. It cannot be ruled out that, in combination with genetic and immunological disorders, fungi can contribute to the initiation of the disease process and perpetuation of active inflammation.The aim of this study was to determine if there are quantitative differences in Candida fungi between pediatric patients with Crohn's disease (before and after exclusive enteral nutrition (EEN), and the biologic therapy with anti-tumor necrosis factor alpha ­ (IFX)), and healthy controls. DNA was isolated from fecal samples and PCR was used to determine the number of fungal cells. Both therapeutic interventions resulted in a statistically significant decrease in Pediatric Crohn's Disease Activity Index. The numbers of Candida decreased during both therapeutic intervention but the difference was statistically significant for the IFX intervention only (p = 0.045). Moreover, fungi population in both study groups declined during intervention when compared to the control group but the difference was significant before treatment only in the IFX group (p = 0.013). The total distribution of Candida with both IFX and EEN as well as in the control group differed significantly (p = 0.01) before treatment only. No correlation between the numbers of Candida and disease activity as well as the following biochemical parameters: serum iron concentration, protein or glucose level were found. It cannot be ruled out that, in combination with genetic and immunological disorders, fungi can contribute to the initiation of the disease process and perpetuation of active inflammation.

Differences in the intestinal microbiome of healthy children and patients with newly diagnosed Crohn's disease.

The aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn's disease (CD) differs among published studies depending on patients' age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy. Stool samples were obtained from controls and newly diagnosed patients prior to any intervention. Microbiota was analysed by 16SrRNAnext-generation-sequencing (NGS). Differences in the within-sample phylotype richness and evenness (alpha diversity) were detected between controls and patients. Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister). Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10-27.7 points), moderate (27.5-40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.

Prognostic value of assessment of stool and serum IL-1ß, IL-1ra and IL-6 concentrations in children with active and inactive ulcerative colitis.

INTRODUCTION: Interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) contribute to the pathogenesis of ulcerative colitis (UC). The aim of our study was to evaluate the serum and stool IL-1ß, IL-1ra and IL-6 concentrations as potential prognostic factors in children with UC. MATERIAL AND METHODS: Thirty-eight children with UC (20 active, 18 inactive) and 14 healthy controls were prospectively included in the study. IL-1ß, IL-1ra and IL-6 concentrations were measured in serum and stool supernatants at inclusion to the study using ELISA immunoassays. The children were followed up over 5 years, and at each follow-up clinical disease activity, quantity and severity of relapses, nutritional status, endoscopic and histopathologic activity, disease complications and the treatment regimen were evaluated. RESULTS: In children with active and inactive UC who had relapsed during a 5-year follow-up period compared to the non-relapse groups we found significantly increased serum IL-1ß (1.34 vs. 0.98 pg/ml, p < 0.05, and 1.02 vs. 0.68 pg/ml, p < 0.01, respectively,) and IL-1ra (718.0 vs. 453.2 pg/ml, p < 0.05, and 567.4 vs. 365.1 pg/ml, p < 0.01, respectively). Additionally, in children who had experienced complications during a 5-year follow-up period we observed significantly increased serum and stool IL-1ß (p < 0.05) and serum IL-1ra (p < 0.01) compared to the group without complications. CONCLUSIONS: We concluded that serum IL-1ß and IL-1ra and to a lesser extend stool IL-1ß concentrations may be useful prognostic factors in children with active and inactive UC over a short-term follow-up period, which may help to identify children that require more aggressive therapy due to an increased risk of relapse or complications resulting from UC.