Reducing Immunoreactivity of Gluten Peptides by Probiotic Lactic Acid Bacteria for Dietary Management of Gluten-Related Diseases.

Immunoreactive gluten peptides that are not digested by peptidases produced by humans can trigger celiac disease, allergy and non-celiac gluten hypersensitivity. The aim of this study was to evaluate the ability of selected probiotic strains to hydrolyze immunoreactive gliadin peptides and to identify peptidase-encoding genes in the genomes of the most efficient strains. Residual gliadin immunoreactivity was measured after one- or two-step hydrolysis using commercial enzymes and bacterial peptidase preparations by G12 and R5 immunoenzymatic assays. Peptidase preparations from Lacticaseibacillus casei LC130, Lacticaseibacillus paracasei LPC100 and Streptococcus thermophilus ST250 strains significantly reduced the immunoreactivity of gliadin peptides, including 33-mer, and this effect was markedly higher when a mixture of these strains was used. In silico genome analyses of L. casei LC130 and L. paracasei LPC100 revealed the presence of genes encoding peptidases with the potential to hydrolyze bonds in proline-rich peptides. This suggests that L. casei LC130, L. paracasei LPC100 and S. thermophilus ST250, especially when used as a mixture, have the ability to hydrolyze immunoreactive gliadin peptides and could be administered to patients on a restricted gluten-free diet to help treat gluten-related diseases.

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.

Diagnosis, Clinical Presentation and Management of Celiac Disease in Children and Adolescents in Poland.

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals, affecting about 1% of the general population in the developed world. In 2012, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommendations for CD diagnoses in children and adolescents were introduced, allowing the "no-biopsy" approach if certain criteria were met. This approach was also confirmed in the revised guidelines published in 2020. Thus, the aim of this study was to assess-over a one-year period-the clinical presentations and current status of the management of children and adolescents diagnosed with CD in Poland. Medical records of children and adolescents, newly diagnosed with CD in 2022/2023 in three medical centers in Poland, were involved. Gastroenterologists completed the specific anonymous web-based forms developed in the CD SKILLS project, including data routinely assessed at individual visits about the diagnostic approach and clinical presentation of the disease. Our study assessed 100 patients (56% girls) with an age range 1.6-18.0 years. We found that 98% of patients were serologically tested prior to a CD diagnosis and 58% of patients were diagnosed using the "no-biopsy" approach. In the analyzed group, 40% belonged to a known risk group, only 22% had annual screening before the CD diagnosis (the longest for 9 years), and 19% showed no symptoms at the time of the CD diagnosis. Our research confirmed the applicability of the "no-biopsy" approach for the diagnosis of CD in children and adolescents in Poland, and also showed changes in the clinical picture of CD. Moreover, we highlight the need to introduce broad CD serological screening in risk groups of the Polish population.

Identification of ATM-dependent long non-coding RNAs induced in response to DNA damage.

DNA damage response (DDR) is a complex process, essential for cell survival. Especially deleterious type of DNA damage are DNA double-strand breaks (DSB), which can lead to genomic instability and malignant transformation if not repaired correctly. The central player in DSB detection and repair is the ATM kinase which orchestrates the action of several downstream factors. Recent studies have suggested that long non-coding RNAs (lncRNAs) are involved in DDR. Here, we aimed to identify lncRNAs induced upon DNA damage in an ATM-dependent manner. DNA damage was induced by ionizing radiation (IR) in immortalized lymphoblastoid cell lines derived from 4 patients with ataxia-telangiectasia (AT) and 4 healthy donors. RNA-seq revealed 10 lncRNAs significantly induced 1 h after IR in healthy donors, whereas none in AT patients. 149 lncRNAs were induced 8 h after IR in the control group, while only three in AT patients. Among IR-induced mRNAs, we found several genes with well-known functions in DDR. Gene Set Enrichment Analysis and Gene Ontology revealed delayed induction of key DDR pathways in AT patients compared to controls. The induction and dynamics of selected 9 lncRNAs were confirmed by RT-qPCR. Moreover, using a specific ATM inhibitor we proved that the induction of those lncRNAs is dependent on ATM. Some of the detected lncRNA genes are localized next to protein-coding genes involved in DDR. We observed that induction of lncRNAs after IR preceded changes in expression of adjacent genes. This indicates that IR-induced lncRNAs may regulate the transcription of nearby genes. Subcellular fractionation into chromatin, nuclear, and cytoplasmic fractions revealed that the majority of studied lncRNAs are localized in chromatin. In summary, our study revealed several lncRNAs induced by IR in an ATM-dependent manner. Their genomic co-localization and co-expression with genes involved in DDR suggest that those lncRNAs may be important players in cellular response to DNA damage.

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.

Celiac-the lone horse? An autoimmune condition without signals of microbiota dysbiosis.

Accumulating evidence supports the role of microbiota in autoimmune processes, but research regarding the role of the gut microbiota in celiac disease (CD) is still emerging, and a consistent CD-associated dysbiosis pattern has not yet been defined. Here, we characterized the microbiota of children newly diagnosed with CD, with their unaffected family members as a healthy control group to reduce confounding factors including genetic background, hygiene, dietary habits, and environment, and followed children with CD over 1 year of dietary intervention (exclusion of gluten) to understand if the microbiota is associated with CD and its mediation. We did not find differences in the microbiota of siblings with and without CD, despite a wealth of evidence in the literature supporting CD-specific microbiota. CD is common among first-degree relatives, so this could suggest that unaffected family members in this study may be living in a pre-CD state, currently below clinical detection. Interestingly, despite the effectiveness of diet in CD control, we did not observe diet-mediated microbiota changes, except for short-term increase in Akkermansia muciniphila. This lack of effect could suggest a very strong CD microbial signature even when controlled or could be a technical shortcoming. Expanded future studies with both related and unrelated controls and diet interventions in both the CD and control arms can provide further context to our findings. IMPORTANCE The microbiota is the community of microbes that live in and on us. These microbes are essential to our health and everyday function. Disruption of the community is associated with diseases ranging from metabolic syndrome to autoimmune diseases to mental disorders. In the case of celiac disease (CD), research remains inconclusive regarding implications of the microbiota in etiology. Here, we compared microbiota of children with CD to those of their unaffected family members and found very few differences in microbiota profiles. We next examined how gluten elimination in CD patients affects the microbiota. Surprisingly, despite diet adherence, microbiota shifts were minimal, with only a short-term increase in Akkermansia muciniphila. Previous studies suggest that family members of CD patients may be living in a pre-CD state, which could explain their microbial similarity. A larger study with unrelated controls and increased microbiota monitoring during diet intervention should give our findings more perspective.

The Occurrence of Gluten-Related Antibodies, Sensitization to Selected Food Allergens, and Antibodies against Intrinsic Factor in Adult Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) autoantibodies, anti-deamidated gluten peptide (DGP) antibodies, specific immunoglobulin E antibodies (sIgE) to selected food allergens, and anti-intrinsic factor (IF) autoantibodies in adult patients with diarrhea-predominant IBS (IBS-D). The study involved 244 patients (170 women) aged 18-75 years. The antibodies were measured with the use of multiparametric immunoassays. Elevated antibody concentrations, irrespective of the class of tested antibody, occurred in 44 patients (17.6%), including 11 patients (4.5%) with positive DGP antibodies, four patients (1.6%) with TTG2 autoantibodies, six patients (2.5%) with IF autoantibodies, and 31 patients (12.7%) with sIgE to food allergens. Sensitization to gluten, proteins from cow's milk, and bovine serum albumin was found in 2.1%, 5.3%, and 9.0% of patients, respectively. Our study showed a high percentage of positive results for the tested antibodies in the IBD-D patients, which indicates the need to perform serological tests for CD, food allergies, and AIG in this group of patients.

The Efficacy and Safety of Single-Strain Probiotic Formulations Containing Bifidobacterium lactis or Bacillus coagulans in Adult Patients with Irritable Bowel Syndrome-A Randomized Double-Blind Placebo-Controlled Three-Arm Interventional Trial.

Probiotics offer a potential new therapeutic approach for irritable bowel syndrome (IBS), but current results are still controversial. The aim of this study was to assess the efficacy and safety of single-strain probiotic formulations in adult IBS patients and to compare the effects of Bifidobacterium lactis NORDBIOTIC™ BI040 (DSM 33812/34614) and Bacillus coagulans NORDBIOTIC™ BC300 (DSM 33836) in a prospective three-arm interventional randomized double-blind placebo-controlled clinical trial. The study included 123 IBS subjects diagnosed according to the Rome IV criteria. The primary outcomes were changes in symptom severity and symptom improvement as assessed using the IBS Severity Scoring System (IBS-SSS) after 4, 8, and 12 weeks of intervention and after 4 weeks of follow-up. Secondary outcomes included the assessment of individual IBS symptoms and the occurrence of adverse events. During the 12-week intervention, IBS-SSS scores significantly decreased (p-values < 0.001) in the study groups but differences between the interventional and placebo groups did not reach statistical significance. However, at the 16th week of follow-up, a significant improvement in the total IBS-SSS score in comparison to the placebo group (20.5%) was found in 43.8% and 52.9% of the Bifidobacterium lactis (p = 0.038, OR 3.0, [95% CI 1.1-8.6]) and the Bacillus coagulans (p = 0.005, OR 4.6 [95% CI 1.5-12.2]) groups, respectively. Bifidobacterium lactis had a beneficial effect on the intensity and frequency of pain, whereas Bacillus coagulans decreased the bowel dissatisfaction. Both strains increased the percentage of patients with normal stool consistency, but only Bifidobacterium lactis induced a decrease in the number of patients with constipation after 6 weeks of supplementation. Both probiotic strains were well tolerated, without differences in the occurrence of adverse events between groups. In conclusion, single-strain supplementation was safe and efficient in IBS patients but showed a different range of effects. Bifidobacterium lactis BI040 primarily reduced the frequency and intensity of pain, while Bacillus coagulans BC300 increased bowel satisfaction [ClinicalTrials.gov NCT05064930].

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.

Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients-The Effect of Disease Duration.

Biochemical abnormalities in the course of type 1 diabetes (T1D) may cause the production/activation of various proteins and peptides influencing treatment and causing a risk of complications. The aim of this study was to assess concentrations of selected serum substances involved in the pathogenesis and course of T1D and to correlate their concentrations with the duration of T1D. The study included patients with T1D (n = 156) at the age of 3-17, who were divided according to the duration of the disease into those newly diagnosed (n = 30), diagnosed after 3-5 (n = 77), 6-7 (n = 25), and over 7 (n = 24) years from the onset of T1D, and age-matched healthy controls (n = 30). Concentrations of amylin (IAPP), proamylin (proIAPP), catestatin (CST), chromogranin A (ChgA), nerve growth factor (NFG), platelet-activating factor (PAF), uromodulin (UMOD), and intestinal fatty acid binding protein (I-FABP) were measured in sera using immunoenzymatic tests. There were significant differences in concentrations of all the substances except UMOD and NGF between T1D patients and healthy children. The duration of the disease affected concentrations of CST, ChgA, PAF, and NGF, i.e., proteins/peptides which could have an impact on the course of T1D and the development of complications. In long-term patients, a decrease in concentrations of CST and ChgA, and an increase in PAF concentrations were found. In the case of NGF, a decrease was observed after the initial high values, followed by an increase over 7 years after T1D diagnosis. Concluding, the results show that concentrations of selected serum indicators may change in the course of T1D. Further studies are needed to establish whether these indicators could be used in the context of predicting long-term complications.

Improved Quantitative Real-Time PCR Protocol for Detection and Quantification of Methanogenic Archaea in Stool Samples.

Methanogenic archaea are an important component of the human and animal intestinal microbiota, and yet their presence is rarely reported in publications describing the subject. One of the methods of quantifying the prevalence of methanogens is quantitative real-time PCR (qPCR) of the methanogen-specific mcrA gene, and one of the possible reasons for detection failure is usually a methodology bias. Here, we refined the existing protocol by changing one of the primers and improving the conditions of the qPCR reaction. As a result, at the expense of a slightly lower yet acceptable PCR efficiency, the new assay was characterized by increased specificity and sensitivity and a wider linear detection range of 7 orders of magnitude. The lowest copy number of mcrA quantified at a frequency of 100% was 21 copies per reaction. The other validation parameters tested, such as reproducibility and linearity, also gave satisfactory results. Overall, we were able to minimize the negative impacts of primer dimerization and other cross-reactions on qPCR and increase the number of not only detectable but also quantifiable stool samples-or in this case, chicken droppings.

The Opinion of Polish Coeliac Patients on the Knowledge of Medical Professionals and Support Groups about Coeliac Disease-A Pilot Study.

A high quality of knowledge and how it is communicated by healthcare professionals (HCPs) let the patient understand coeliac disease (CD) and result in better adherence to therapeutic recommendations. Therefore, the aim of the current study was to assess the opinion of Polish respondents with CD on the comprehension of CD among Polish HCPs. The analysis was based on 796 responses from patients (the members of the Polish Coeliac Society) with confirmed CD diagnosis (224; 28.1% children and 572; 71.9% adults). The most frequently consulted HCPs regarding CD symptoms in the analysed group were gastroenterologists, and various support groups and associations for CD patients. Furthermore, their comprehension of CD was rated best, as 89.3% (n = 552) of the patients who had contact with support groups and associations classified their knowledge on CD as good. More than a half of the respondents (n = 310, 56.6%) who had contact with general practitioners (GPs) due to their symptoms, rated the doctor's knowledge on CD as bad. Nurses' comprehension on CD was classified as bad by 45 (52.3%) respondents who had contact with a nurse. Out of 294 Polish patients with CD who had contact with a dietician, 247 (84.0%) assessed that the dietician communicated their knowledge on CD well. The respondents rated that GPs and nurses communicated their knowledge on CD in the worst manner (60.4% and 58.1%, respectively). Out of 796 respondents, 792 (99.5%) provided information about the number of appointments with GPs due to symptoms that occurred prior to CD diagnosis. The respondents had contact with GPs 13 863 times before obtaining a CD diagnosis due to their symptoms. After the establishment of a CD diagnosis, the number of appointments with GPs decreased to 3850, and the average number of appointments decreased from 17.8 to 5.1. The respondents assessed that the knowledge on CD of HCPs is not satisfactory. The work of support groups and associations on CD, who promote reliable CD diagnosis and treatment methods, should be promoted. The cooperation between various HCPs needs to be encouraged, which may lead to better compliance.

Allergic March in Children: The Significance of Precision Allergy Molecular Diagnosis (PAMD@) in Predicting Atopy Development and Planning Allergen-Specific Immunotherapy.

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3-5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient's allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results.

IgE-Dependent Allergy in Patients with Celiac Disease: A Systematic Review.

In order to answer the question if an IgE-mediated allergy (A-IgE) may occur in subjects with celiac disease (CD), a systematic review was performed of available publications collected in the United States National Institute for Biotechnology Information/National Institutes of Health/National Library of Medicine/PubMed database up to 28 December 2022, with the use of the following keywords "allergy&celiac/coeliac", "sensitization&celiac/coeliac", and "anaphylaxis&celiac/coeliac" compared in the form of a conjunction. In total, the search returned 2013 publications from these keywords in any section of the article. As numerous review articles included the above-mentioned entries in the abstract, we decided to focus on the publications with the entries only in the title (n = 63). After rejecting studies unrelated to the topic, narrative reviews, book chapters, conference abstracts, symposium reports, letters to the editor, or non-English articles, 18 publications (6 observational original studies and 12 case reports describing a total of 15 cases of A-IgE developed after a diagnosis of CD) were included to this review. Our study is the first systematic review on allergy occurrence in CD patients. The analysis indicated that the possibility of a coexistence of A-IgE with any food and inhalant allergens in subjects diagnosed with CD should be considered. A sensitization to wheat was the most frequently described in subjects with CD. The clinical manifestation of A-IgE in CD was similar to that in subjects without CD; e.g., with possible atopic dermatitis, vomiting, urticaria, angioedema, or anaphylactic shock. Screening for allergies in subjects with CD should be considered, especially in those cases where symptoms persist after introducing a gluten-free diet. The elimination of wheat from the diet of patients with CD may lead to a loss of immune tolerance and to the development of sensitization, which may even manifest as anaphylaxis. In conclusion, although there are few studies assessing the occurrence of A-IgE in subjects with CD, they show the possibility of a coexistence of both diseases and the high clinical significance of this phenomenon, which indicates the need for further studies.

Prevalence and Significance of Autoantibody Seropositivity in Children with Wilson's Disease.

Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE.

The Impact of a CMV Infection on the Expression of Selected Immunological Parameters in Liver Tissue in Children with Biliary Atresia.

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm2 of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm2 in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA.

Effects of Microencapsulated Sodium Butyrate, Probiotics and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome: A Study Protocol of a Randomized Double-Blind Placebo-Controlled Trial.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease in the pathogenesis of which gut dysbiosis may play an important role. Thus, probiotics, prebiotics, or microbiota metabolites, such as butyric acid, are considered to be effective therapy for IBS. However, there are still no trials presenting the efficacy of these three biotic components administered simultaneously. This study aims to evaluate the effects of the product comprising sodium butyrate, probiotics, and short-chain fructooligosaccharides (scFOS) on the severity of clinical IBS symptoms and the quality of life (IBS-QOL). This is a randomized double-blind placebo-controlled trial conducted in 120 adults with IBS diagnosed according to Rome IV criteria. The intervention group (n = 60) will receive a mixture of the following components: 300 mg of colon-targeted microencapsulated sodium butyrate combined with probiotic Lactobacillus strains (L. rhamnosus and L. acidophilus) and Bifidobacterium strains (B. longum, B. bifidum, B. lactis), and 64 mg of prebiotic scFOS. The control group (n = 60) will receive a placebo (maltodextrin). The primary outcomes will be changes in IBS symptoms with the use of the IBS-Severity Scoring System (IBS-SSS), IBS-Global Improvement Scale (IBS-GIS), IBS-Adequate Relief (IBS-AR), and IBS-QOL after 12 weeks of intervention. The secondary outcomes will be the type of stools, patient-recorded symptoms, adverse events, anthropometric and nutritional parameters, and inflammatory cytokine levels. The findings will provide the first evidence of the use of a combination of three biotic compounds in IBS. The study was registered in the clinicaltrials.gov registry under the number NCT05013060.

How to Recognize and Treat Small Intestinal Bacterial Overgrowth?

Small Intestinal Bacterial Overgrowth (SIBO) is a form of dysbiosis that involves increased bacterial colonization of the small intestine with some of the bacteria more characteristic of the colon microbiota. The prevalence of SIBO over recent decades has been estimated to range from 2.5 to 22% (depending on the source) and to increase with age and among individuals with comorbidities. Recently, an increase in the number of diagnosed SIBO cases has been observed, which is primarily due to the availability of noninvasive breath tests that facilitate the diagnostic process. However, SIBO is still both a diagnostic and a therapeutic problem. This review presents the pathophysiology, manifestations, diagnostics, and recommended management of SIBO.

The Precision Allergy Molecular Diagnosis (PAMD@) in Monitoring the Atopic March in a Child with a Primary Food Allergy: Case Report.

The case of a 9-month-old boy with an initial diagnosis of atopic dermatitis and confirmed allergy to hen's egg, cow's milk allergens with episodes of anaphylaxis who developed birch allergy whilst under observation with asthma symptoms was presented. The precision allergy molecular diagnosis (PAMD @) allowed for individualisation of dietary recommendations and observing the early progression of food sensitisation to the main birch molecule. The presented identification of major allergic molecules with PAMD@ in the preclinical phase of asthma contributes to the discussion related to early specific immunotherapy to suppress molecular spread and allergic march. However, more research is needed to verify this hypothesis.

New non-invasive biomarkers of intestinal inflammation and increased intestinal permeability in pediatric inflammatory bowel diseases and their correlation with fecal calprotectin: a pilot study.

BACKGROUND: Increased intestinal permeability is considered to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBD). Therefore, recently, the use of non-invasive biomarkers in both diagnosis and monitoring IBD is emphasized. The aim of this study was to investigate fecal and serum zonulin and serum I-FABP in pediatric IBD patients and their correlation with fecal calprotectin (FCP). METHODS: Seventy-one individuals: 32 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients and 6 controls were examined for fecal and serum zonulin and plasma I-FABP. Values were correlated to FCP and to each other for all children included in the study. A stool specimen and blood samples were collected during check-up visits at hospital. Then fecal and serum zonulin, I-FABP and FCP were tested by ELISA test. Non-parametric statistical tests were used for data analysis. RESULTS: The level of fecal zonulin and FCP were higher in IBD patients compared to control group (CG): median for CD - 46.0 (7.0-3854) ng/mL, 252.0 (77.0 -1054.2) ug/g; UC - 115.3 (50.7-418.3) ng/mL, 40 (16.0-1883.0) ug/g; CG - 60.8 (31.8-123.0) ng/mL, 41.5 (31.0-323.0) ug/g, respectively, (P<0.05). No statistically significant difference in concentrations of serum zonulin and I-FABP was reported between patients and CG (P=0.55). The only correlation that has been reported was between fecal zonulin and FCP and the strongest one was in CD: CD - R = 0.73, UC - R = 0.67, All - R=0.67, CG - R=0.65. CONCLUSIONS: According to our results it seems that only fecal zonulin may serve as another, next to FCP, biomarker of intestinal damage in IBD. However, both fecal and serum zonulin as well as IFABP need further studies to assess their usefulness in diagnostics and monitoring in IBD.