Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

The Sensitization Profile for Selected Food Allergens in Polish Children Assessed with the Use of a Precision Allergy Molecular Diagnostic Technique.

Individual populations show a variety of sensitization patterns, which may be associated with the geographic region, climate, dietary habits, or ways of preparing food. The purpose of this study was to comprehensively assess the food allergy sensitization profile in Polish children, particularly to eight food allergens (so-called "the Big 8"): cow milk, eggs, wheat, soybeans, fish, crustacean shellfish, tree nuts, and peanuts. To assess the prevalence and serum levels of specific immunoglobulins E (sIgE), we analyzed the results obtained from selected laboratories located in all regions of Poland that used the multiplex ALEX® test in the period from 2019 to 2022. Results from 3715 children were obtained. The mean age of the study population was 7.0 years. The results were stratified by age: <12 months (3.63%), 1-5 years (39.54%), 6-13 years (46.32%), and 14-18 years (10.0%). The final analysis included the sIgE results obtained with 95 food extracts and 77 food allergen molecules. The highest rates of sIgE to food allergen extracts were found for peanut (29.20%), hazel (28.20%), and apple (23.60%), and those to allergenic molecules were found for the PR-10 family of molecules (Cor a 1.0401 (23.77%), Mal d 1 (22.37%), Ara h 8 (16.93%), and globulin 7/8S (Ara h 1; 15.59%)). The lowest rates of sIgE reactivity to extracts were found for strawberry (0.40%), oregano (0.30%), and thornback ray (0.16%), and those to allergenic molecules were found for Mal d 2 (0.27%) (thaumatin-like protein, TLP), Ani s 1 (0.30%) (Kunitz-type serine protease inhibitor), and Che a 1 (0.43%) (Ole e 1 family). The rates of sensitization to storage proteins of the analyzed "the Big 8" molecules decreased significantly (p < 0.05) with age. Conversely, the rates of sensitization to PR-10 family proteins increased significantly with age. The three most common allergens in Poland, regardless of whether IgE was assayed against extracts or molecules of food allergens, were peanut, hazel, and apple (in different order depending on the ranking). A detailed analysis of sensitization to the extracts and molecules of main food allergens based on the results of a multiplex ALEX® test demonstrated the sensitization profile in Polish children (including molecular sensitization, particularly the "the Big 8" food allergen molecules), which shows considerable differences in comparison with those in other countries. Serum sIgE analysis of children from all regions of Poland revealed a food allergen molecular sensitization profile that changes with age.

Mosaic IL6ST variant inducing constitutive GP130 cytokine receptor signaling as a cause of neonatal onset immunodeficiency with autoinflammation and dysmorphy.

Interleukin-6 signal transducer (IL6ST) encodes the GP130 protein which transduces the proinflammatory signaling of the IL6 cytokine family through Janus kinase signal transducers and activators of transcription pathway (JAK/STAT) activation. Biallelic loss-of-function IL6ST variants cause autosomal recessive hyper-IgE syndrome or a variant of the Stuve-Wiedemann syndrome. Somatic gain-of-function IL6ST mutations, in particular, small monoallelic in-frame deletions of which the most prevalent is the IL6ST Ser187_Tyr190del, are an established cause of inflammatory hepatocellular tumors, but so far, no disease caused by such mutations present constitutively has been described. Herein, we report a pediatric proband with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphy associated with the IL6ST Tyr186_Tyr190del variant present constitutively. Tyr186_Tyr190del was found by exome sequencing and was shown to be de novo (absent in proband's parents and siblings) and mosaic (present in approximately 15-40% of cells depending on the tissue studied-blood, urine sediment, hair bulbs and buccal swab). Functional studies were performed in the Epstein-Barr virus-immortalized patient's B cell lymphoblastoid cell line, which carried the variant in approximately 95% of the cells. Western blot showed that the patient's cells exhibited constitutive hyperphosphorylation of Tyr705 in STAT3, which is indicative of IL6-independent activation of GP130. Interestingly, the STAT3 phosphorylation could be inhibited with ruxolitinib as well as tofacitinib, which are clinically approved JAK1 and JAK3 (to lesser extent JAK2 and JAK1) inhibitors, respectively. Given our results and the recent reports of ruxolitinib and tofacitinib use for the treatment of diseases caused by direct activation of STAT3 or STAT1, we speculate that these drugs may be effective in the treatment of our patient's condition.

Microorganisms Involved in Hydrogen Sink in the Gastrointestinal Tract of Chickens.

Hydrogen sink is a beneficial process, which has never been properly examined in chickens. Therefore, the aim of this study was to assess the quantity and quality of microbiota involved in hydrogen uptake with the use of real-time PCR and metagenome sequencing. Analyses were carried out in 50 free-range chickens, 50 commercial broilers, and 54 experimental chickens isolated from external factors. The median values of acetogens, methanogens, sulfate-reducing bacteria (SRB), and [NiFe]-hydrogenase utilizers measured in the cecum were approx. 7.6, 0, 0, and 3.2 log10/gram of wet weight, respectively. For the excreta samples, these values were 5.9, 4.8, 4, and 3 log10/gram of wet weight, respectively. Our results showed that the acetogens were dominant over the other tested groups of hydrogen consumers. The quantities of methanogens, SRB, and the [NiFe]-hydrogenase utilizers were dependent on the overall rearing conditions, being the result of diet, environment, agrotechnical measures, and other factors combined. By sequencing of the 16S rRNA gene, archaea of the genus Methanomassiliicoccus (Candidatus Methanomassiliicoccus) were discovered in chickens for the first time. This study provides some indication that in chickens, acetogenesis may be the main metabolic pathway responsible for hydrogen sink.

The impact of symptoms on quality of life before and after diagnosis of coeliac disease: the results from a Polish population survey and comparison with the results from the United Kingdom.

BACKGROUND: Coeliac disease (CD) is characterised by diverse clinical symptoms, which may cause diagnostic problems and reduce the patients' quality of life. A study conducted in the United Kingdom (UK) revealed that the mean time between the onset of coeliac symptoms and being diagnosed was above 13 years. This study aimed to analyse the diagnostic process of CD in Poland and evaluate the quality of life of patients before and after CD diagnosis. In addition, results were compared to the results of the original study conducted in the UK. METHODS: The study included 2500 members of the Polish Coeliac Society. The patients were asked to complete a questionnaire containing questions on socio-demographic factors, clinical aspects and quality of life, using the EQ-5D questionnaire. Questionnaires received from 796 respondents were included in the final analysis. RESULTS: The most common symptoms reported by respondents were bloating (75%), abdominal pain (72%), chronic fatigue (63%) and anaemia (58%). Anaemia was the most persistent symptom, with mean duration prior to CD diagnosis of 9.2 years, whereas diarrhoea was observed for the shortest period (4.7 years). The mean duration of any symptom before CD diagnosis was 7.3 years, compared to 13.2 years in the UK. CD diagnosis and the introduction of a gluten-free diet substantially improved the quality of life in each of the five EQ-5D-5L health dimensions: pain and discomfort, anxiety and depression, usual activities, self-care and mobility (p < 0.001), the EQ-Index by 0.149 (SD 0.23) and the EQ-VAS by 30.4 (SD 28.3) points. CONCLUSIONS: Duration of symptoms prior to the diagnosis of CD in Poland, although shorter than in the UK, was long with an average of 7.3 years from first CD symptoms. Faster CD diagnosis after the onset of symptoms in Polish respondents may be related to a higher percentage of children in the Polish sample. Introduction of a gluten-free diet improves coeliac patients' quality of life. These results suggest that doctors should be made more aware of CD and its symptoms across all age groups.

Fatty Acid-Binding Protein 1 as a Potential New Serological Marker of Liver Status in Children With Wilson Disease.

OBJECTIVES: Wilson disease (WD) is a copper metabolism disorder with toxic copper accumulation in the liver leading to liver steatosis or fibrosis. In vitro studies suggest that fatty acid-binding protein 1 (L-FABP) and lipid droplet-associated protein 5 (PLIN5) may have an impact on both processes, but knowledge about these potential biomarkers is insufficient in the case of WD. Thus, the aim of this study was to determine L-FABP and PLIN5 levels in sera of WD patients in relation to liver steatosis/fibrosis. METHODS: The final study involved 74 WD children in whom liver steatosis (WD1 subgroup, n = 28) and fibrosis (WD2 subgroup, n = 13) were assessed with the use of transient elastography. Control groups included WD children without steatosis and fibrosis (WD0 subgroup, n = 33) and healthy children (n = 75). L-FABP and PLIN5 measurements were performed in sera with the use of the immunoenzymatic method. RESULTS: L-FABP was significantly higher in the WD2 subgroup, and the correlation between L-FABP concentration and liver fibrosis was confirmed statistically by regression analysis (P = 0.04) with Pearson's coefficient r = 0.24. L-FABP was significantly correlated with alanine aminotransferase (r = 0.42) and aspartate aminotransferase (r = 0.37) activity. PLIN5 concentration was similar in all groups and was not related to steatosis and fibrosis. CONCLUSIONS: Our results suggest that serum L-FABP could be a novel biomarker of liver fibrosis in WD children.

The potential association between a new angiogenic marker fractalkine and a placental vascularization in preeclampsia.

PURPOSE: Impaired angiogenesis is one of the most common findings in preeclamptic placentas. A new angiogenetic role of fractalkine (CX3CL1) is recently recognized apart from inflammatory activity. In this study, a link between CX3CL1 and the development of placental vasculature in preeclampsia was examined. METHODS: The study comprised 52 women allocated to Group 1 (normotensive, n = 23) and Group 2 (preeclampsia, n = 29). In each group Doppler parameters, serum levels of CX3CL1, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) were assessed between 30 and 32 week of pregnancy. After the delivery, placental samples were taken and the vascularization and expression of CX3CR1 receptor were assessed after immunostaining. RESULTS: CX3CL1 and sFlt-1 serum levels were significantly higher levels in Group 2 vs Group 1, while PlGF serum levels was significantly lower in Group 2. Lower cerebroplacental ratio (CPR) was observed in Group 2. The vascular/extravascular tissue index (V/EVTI) was significantly lower in Group 2, while compared to Group 1, with the lowest value in the fetus growth restriction (FGR) subgroup (0.18 ± 0.02; 0.24 ± 0.03; 0.16 ± 0.02, respectively). The expression of examined CX3CR1 was higher in Group 2, while compared to Group 1, reaching the highest values in FGR subgroup. There was a moderate negative correlation between birth weight, V/EVTI and CX3CL1 serum level and CX3CR1 placental expression in the group of pregnancies complicated with preeclampsia. CONCLUSION: The significant underdevelopment of placental vascular network in preeclampsia is associated with the change in the CX3CL1/CX3CR1 system, especially in FGR complicated pregnancies.

Medulloblastoma with transitional features between Group 3 and Group 4 is associated with good prognosis.

Medulloblastoma, the most common malignant pediatric brain tumor, is a heterogeneous disease, with the existence of at least four molecular types: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 and Group 4 tumors. The latter two groups, which can be identified by an application of multi-gene expression or methylation profiling, show sometimes ambiguous categorization and are still classified for diagnostic reason as non-SHH/non-WNT medulloblastomas in updated WHO 2016 classification. In order to better characterize non-SHH/non-WNT tumors, we applied the method based on the Nanostring nCounter Technology, using the 26 genes codeset in 68 uniformly treated medulloblastoma patients. This allowed for identification of tumors, which shared common Group 3 and Group 4 gene signatures. We recognized three transcriptional groups within non-WNT/non-SHH tumors: Group 3, Group 4 and the Intermediate 3/4 Group. Group 3, in line with previously published results, showed poor prognosis with survival rate < 40%, frequent metastases, large cell/anaplastic pathology and presence of tumors with MYCC amplification. This is in contrast to patients from the Intermediate 3/4 Group who showed the best survival rate (100%). Overall and progression free survival were better for this group than for Group 3 (p = 0.001, for both) and Group 4 (p = 0.064 and p = 0.066, respectively). Our work supports the view that within the non-WNT/non-SHH tumors different risk groups exist and that the current two groups classifier may be not sufficient for proper clinical categorization of individual patients.

Oxidative and Antioxidative Stress Status in Children with Inflammatory Bowel Disease as a Result of a Chronic Inflammatory Process.

Oxidative stress (OS) has been recently implicated in the disease pathogenesis in inflammatory bowel disease (IBD). The aim of the study was to evaluate oxidative and antioxidative stress status and the risk of the atherosclerotic process in children with IBD and functional gastrointestinal disorders (FGID). The prospective study included a group of 71 children during a period of 2 years. In all children, laboratory tests were performed and intima-media complex in the carotid artery was measured (IMC). Low values of OS were more frequent in children with IBD than in the FGID group. The average concentration of oxidized lipoprotein with average density (oxLDL) was lower in patients with IBD. Among patients with IBD, higher concentrations of oxLDL were recorded in patients with longer-duration disease and with higher concentrations of total cholesterol. In the IBD group, more often, higher concentrations of anti-oxLDL were recorded among patients with longer-duration disease. The obtained results did not support the hypothesis of total antioxidant capacity depletion and greater overall OS in patients with IBD. Patients with IBD with a longer duration of the disease have higher concentrations of oxLDL and anti-oxLDL.

[Celiac disease - disease of children and adults: symptoms, disease complications, risk groups and comorbidities]. / Celiakia ­ choroba dzieci i doroslych: objawy, powiklania, grupy ryzyka i choroby wspólistniejace.

About 1% of human population suffers from celiac disease (CD) and it is one of the most commonly diagnosed autoimmune disorders. Until recently it was believed that CD affects mainly children, but as the newest studies show, up to 60% recently diagnosed patients are adults, often over the age of 60. CD's medical signs are nonspecific. Atypical course of the disease with extraintestinal symptoms is being increasingly observed. The disease may also be asymptomatic over many years. The studies show that the average diagnosis of CD takes more than 10 years since the first symptoms appear. Nonspecific medical signs cause undiagnosed patients suffering from CD to visit gastroenterologists, endocrinologists, allergists, gynaecologists and other medical specialists. However, most frequently general practitioners have the first encounter with patients suffering from CD, therefore they are able to recognize symptoms of the disease at the earliest and refer the patient to a gastroenterologist. Early diagnosis and beginning of the treatment reduce complications of untreated CD. The aim of this paper is to show general practitioners symptoms, disease complications, risk groups and comorbidities of CD.

Autophagy in Hepatocytes in Infants With Alpha-1 ATD and Different Liver Disease Outcomes: A Retrospective Analysis.

OBJECTIVES: It is unclear whether a distinct activity of pathways removing the antitrypsin (AT) protein in Alpha-1-Antitrypsin Deficiency (α1ATD) are associated with an unfavorable predisposition to liver disease in the future. The aim of this study was to determine whether liverspecific activity of AT protein disposal occurs at infancy in α1ATD with PiZZ phenotype (ATZ). METHODS: Liver samples of 17 infants with unfavorable ATZ outcome (Group I, n = 8, median age  = 0.35 year) and good outcome (Group II, n = 9, 0.17 year), and 9 with biliary atresia (BA, median age = 0.17 year) as control, were enrolled. For each subject were investigated autophagy activity by mRNA, protein expression (Calnexin, Beclin-1, p62, and Parkin), and hepatocyte ultrastructure with morphometric analyses. RESULTS: No significant differences in gene expression in the liver of infants were found between the 2 ATZ groups. Although a correlation between patients' age and protein expression was observed, the ATZ groups differed Parkin immunohistochemical expression. Moreover, the hepatocytes in ATZ infants with unfavorable outcome were characterized by low Parkin expression and the presence of isolated mitophagosoms and numerous enlarged mitochondria. The mentioned findings differed in patients with BA. CONCLUSIONS: Thus, mentioned specific features occurring at infancy may suggest association with poor liver outcome. Parkin low expression could have a potential for disease prognosis and treatment; however, further studies in a greater number of patients are needed.

Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant.

Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10(-49)), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10(-44)). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10(-49)), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD.

Specific IgE Antibodies in Young Children with Atopic Dermatitis--Correlation of Multiple Allergen Simultaneous Immunoblot Test and ImmunoCap System.

BACKGROUND: Sensitization to food allergens is a common condition in pediatric atopic dermatitis (AD). Recently, the multiple allergen simultaneous test (MAST) allowing for a comprehensive assessment of atopy has been developed, but the usefulness in young AD children is not known. The aim of this study was to determine IgE specificity in AD children using MAST and to compare the results for selected food allergens with the reference ImmunoCap system. METHODS: The study enrolled 50 children up to 2 years old with a diagnosis of AD. IgE antibodies were measured with the MAST-immunoblots. Children with specific IgE levels ≥ 0.35 kU/L were identified as sensitized to allergens. RESULTS: Most often children were sensitized to food allergens (egg white and yolk, hazelnuts, potato, cow's milk proteins, wheat flour, codfish, and soybean), but a high percentage of them also had IgE antibodies against house dust mites (12%), grass (10%), and birch (10%). Eight percent of children were sensitized to domestic animals (cats and dogs). Almost perfect (kappa index 0.8 - 1.0) and substantial (kappa index 0.6 - 0.8) agreement between MAST and ImmunoCap was found for food allergens except codfish. Pearson's analysis of antibody classes showed a very strong correlation between two methods (r = 0.8 - 1.0) for egg white, hazelnuts, potato, cow's milk proteins, wheat flour, and soybean, and a strong correlation (r = 0.6 - 0.79) was observed for peanut, egg yolk, and codfish. CONCLUSIONS: The study showed the frequent occurrence of IgE antibodies against food and airborne and animal allergens in young AD children and confirmed the usefulness of MAST-immunoblots for screening of sensitization in pediatric patients.

Autoantibody Profile of Adult Patients With Childhood Onset Type 2 Autoimmune Hepatitis.

BACKGROUND: Anti-liver kidney microsome (anti-LKM) autoantibodies are a distinguishing feature of type II autoimmune hepatitis (AIH-2). However, the levels of anti-LKM-1 in adult AIH-2 patients and their role in liver immunopathology remain equivocal. The aim of the study was to survey the autoantibody profile and the activity of liver disease in adult patients diagnosed with AIH-2 at childhood. METHODS: The autoantibody profile of adults was compared with the autoantibodies of the pediatric period. Liver function test, Immunoglobulin G (IgG), and gamma globulins were evaluated at the AIH presentation, at the age of 18 years, and at the current adult visit. RESULTS: All ten patients tested positive for LKM-1 at least once during the pediatric period. At the adult visit, four patients lost autoantibody positivity. LKM-1 was positive in four, liver cytosol antigen 1 (LC-1) in two, soluble liver antigen in one, and antinuclear antigen in one patient. Additionally three patients with LKM-1 and one patient without LKM-1 were positive for AMA-M2 (where AMA is antimitochondrial antibodies) Immunoglobulin M (IgM). Liver function markedly improved at 18 years and adult visit compared with initial diagnosis of AIH with only a mild decrease of IgG. The six adult patients positive for at least one autoantibody had statistically lower aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGTP) than the four patients autoantibody negative (AST: 52 vs. 88 IU/l, P < 0.05; GGTP 19 vs. 163 IU/l, P < 0.05). CONCLUSION: LKM-1 positivity is not a stable condition in all patients with AIH-2. Patients who remained autoantibody positive had better liver function tests than those who lost their positivity. The presence of AMA-M2 autoantibodies suggest that development of AIH/Primary Biliary Cirrhosis (PBC) overlap syndrome should be considered.

Contrast enhancement pattern predicts poor survival for patients with non-WNT/SHH medulloblastoma tumours.

Recent studies revealed the biological heterogeneity of medulloblastoma, with the existence of at least four groups which are associated with several clinical and morphological features. We investigated for further correlations between molecular types, location of tumours, their contrast enhancement pattern and survival of patients. Altogether 76 tumours were analyzed and molecular subtypes were identified by immunohistochemistry using representative antibodies, detection of chromosome 6 monosomy and CTNNB1 mutation. The site of the tumour was assessed on diagnosis using Magnetic Resonance images and intra-operative surgical reports. In addition, the gadolinium enhancement pattern was also investigated in pre-treatment tumours. Cerebellar hemispheric location was associated with SHH tumours (p < 0.001), as opposed to midline location being typical for WNT and non-WNT/SHH tumours. Remarkably, for patients with non-WNT/SHH tumours, the extensive gadolinium enhancement pattern (present in >75% of tumour volume) predicted worse OS and EFS than for those with none/weak or heterogeneous enhancement (>10-75% of tumour volume), (both p < 0.001). Our analysis indicates that distribution of the medulloblastoma tumours location is related to the biological characteristics of tumour. Importantly, the enhancement pattern of the tumour may be a clinically useful prognostic marker for patients with non-WNT/SHH medulloblastomas.

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants.

BACKGROUND: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. OBJECTIVE: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. DESIGN: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. RESULTS: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. CONCLUSIONS: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.

Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined) =  1.2 × 10(-12)), rs864537 near CD247 (P(combined) =  2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined) =  2.5 × 10(-10)), and rs11203203 near UBASH3A (P(combined) =  1.1 × 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

Whole-genome sequencing and characterization of human fecal isolate Lacticaseibacillus casei LC130 from NORDBIOTIC collection.

We report the complete genome sequence of Lacticaseibacillus casei LC130, isolated from a healthy human fecal sample and part of the NORDBIOTIC collection. The 2.969 Mb genome of LC130 includes genes potentially involved in lactose metabolism and the production of bacteriocins, peptidases, and polyamines, suggesting potential health benefits.

Complete genome sequence of the probiotic Lacticaseibacillus paracasei LPC100 strain from the NORDBIOTIC collection isolated from a human fecal sample.

We report the genome sequence of the human fecal isolate Lacticaseibacillus paracasei LPC100 from the NORDBIOTIC collection, comprising a 3.075 Mb chromosome and three plasmids (61 kb, 12 kb, and 7 kb). Genetic content reveals the strain's beneficial features-complete lactose metabolic pathway, potential production of bacteriocins, and short-chain fatty acids.

The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review.

Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.