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(1) Background. Coeliac disease (CD) often co-occurs with autoimmune conditions or genetic syndromes, but there are few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies. The purpose of this study was to assess sensitization to food and aero-allergens in pediatric patients with CD. (2) Methods. A multiplex ALEX®2 test was used to determine specific IgEs (sIgEs). (3) Results. The study included 108 children newly diagnosed with CD. Allergen extract- and/or allergen molecule-sIgEs were detected in 49.1% of children. Most children (41.5%) were sensitized to both inhalant and food allergens. The three most common aero-allergens (timothy pollen, ryegrass, silver birch) were molecules Phl p 1, Lol p 1, and Bet v 1. The most common food allergens (hazelnut, apple, and peanut) were Cor a 1, Mal d 1, and Ara h 8 molecules of the PR-10 subfamily. Patients were not sensitized to cereal allergens containing gluten. Spearman’s rank correlation analysis of sensitized patients showed a significant positive relationship (r = 0.31) between the patients’ age and the occurrence of positive sIgEs (≥0.3 kUA/L) for inhalant allergen molecules (p = 0.045). In sensitized patients, mainly symptoms of inhalant allergy were observed, such as hay fever, conjunctivitis, and bronchial asthma. (4) Conclusions. The current study indicates the co-occurrence of IgE sensitization to food and inhalant allergens in children with CD. The study highlights the need to take a closer look at the diagnosis of IgE-mediated allergy in patients with CD, which may help in their care and lead to a better understanding of the relationship between CD and IgE-mediated allergy.

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.

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.

ABSTRACT 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 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 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.

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: 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.

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].

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.

Introduction: Celiac disease (CD) is an autoimmune disease that affects genetically predisposed individuals. In course of the disease, consumption of gluten causes damage to the small intestine. Due to various clinical manifestations, diagnosing CD poses a challenge to clinicians. It has been proven by several study groups that the diagnostic delay in CD is still too long and provokes severe health complications. Purpose: The aim of the study is to highlight the importance of diagnostic delay in CD, its consequences and possible solutions. Description of the state of knowledge: The diagnosis of CD is based on the clinical picture, serological test, duodenal mucosal biopsies and genetic tests. Many cases of CD remain undiagnosed in spite of published guidelines for CD diagnosis. Consequently, the diagnosis is significantly delayed: the mean duration of the diagnostic process in Poland was 7.3 years. In other countries, patients the time from the onset of the symptoms to establishing CD diagnosis was up to 10 years. The diagnostic delay leads to reduced quality of life and the development of severe complications, such as neoplastic disease. Summary: Diagnostic delay in CD is an issue of great importance. Because of the reduced quality of life and the possibility of neoplasm, it is crucial to take action in order to shorten the diagnostic process of CD.

Abstract 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

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.

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.

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.

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 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.

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.

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.

The diagnosis of celiac disease (CD) at the first diagnostic step requires the detection of specific class A antibodies to tissue transglutaminase type-2 (TG2 IgA) and the measurement of total immunoglobulin A (tIgA) to exclude IgA deficiency. The aim of the study was to evaluate the new quantitative immunoassay panel allowing for the detection of celiac-specific antibodies with the simultaneous determination of tIgA from the same sample of blood at one time. This retrospective study included 104 pediatric patients divided into groups with recognized CD and IgA deficiency (n = 20; 19%), immunocompetent children with CD (n = 28; 27%), children with IgA deficiency and without CD (n = 28; 27%), and the control group of immunocompetent children without CD (n = 28; 27%). Intestinal biopsy with histopathological evaluation (except five patients with CD who were diagnosed without biopsy) and measurement of reference celiac specific antibodies were performed in all children. Multiparametric quantitative immunoassay Polycheck® Celiac IgA plus total IgA test was used to evaluate its usefulness in CD screening and IgA deficiency diagnosis. The statistical analysis showed the high sensitivity and specificity of both TG2 IgA and tIgA on the multiparametric panel (sensitivity 96% and 100%; specificity 100% and 79%, respectively). The accuracy and area under the ROC curve for tIgA were 0.904 and 0.955, while for TG2 IgA they were 0.982 and 1.000, respectively. Although the sensitivity of IgA antibodies against deaminated gliadin peptides was low (20%), the specificity reached 100%. The study showed that Polycheck® Celiac IgA plus total IgA test is a specific and sensitive tool for simultaneous serological CD screening and recognition of IgA deficiency.

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.

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.

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700–0.7690) in comparison with 0.664 (95% CI: 0.632–0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Introduction and Objectives. Celiac disease (CD) is a complex autoimmune disorder occurring in genetically susceptible individuals. There is limited data on the impact of gluten-free diet (GFD) on the risk of developing cardiovascular diseases. Hereby, we present our study regarding the impact of treatment with GFD on the biochemical risk factors of atherosclerosis. Material and Methods. 277 patients with CD from 7 Polish clinics were enrolled in the study (210 children treated for at least 5 years and 67 children included in the study on the day of CD diagnosis and observed for 1 year on a GFD). We obtained selected clinical data, and we assessed lipid profile, apolipoproteins (A1, B, and E), lipoprotein (a), homocysteine, as well as antioxidants (folic and uric acid), and high-sensitivity CRP (hsCRP) for all patients. The compliance to GFD was verified using anti-transglutaminase antibodies and deamidated gliadin peptide antibodies. As a reference group, the data of 95 healthy children recruited for another project was used, for which we had the results of selected parameters. Results. We found significantly lower concentrations of total cholesterol, lipoprotein LDL-C, apolipoproteins A1 and B, as well as hCRP in all children with CD. We showed decreased level (5 years. Moreover, we showed significant decrease of folic acid level already after 1 year of a GFD (12 vs. 5.6 ng/mL; p

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

The diagnosis of celiac disease (CD) may be delayed due to non-specific clinical symptoms. The aim of the study was to evaluate the clinical manifestation and diagnostic process of CD in Polish children and adults. Methods: The members of the Polish Coeliac Society (n = 2500) were asked to complete a questionnaire on socio-demographic factors, clinical and diagnostic aspects of CD. The analysis was based on 796 responses from patients with confirmed CD diagnosis, and included 224 (28.1%) children and 572 (71.9%) adults. Results: The mean duration of symptoms prior to CD diagnosis in children was significantly shorter than in adults (p < 0.001), and amounted to 3.1 and 9 years respectively. The most frequent symptoms before CD diagnosis were abdominal pain and bloating in children (70.4%), and chronic fatigue in adults (74.5%). Although almost all CD patients claimed to strictly avoid gluten after CD diagnosis, symptoms were still present in the majority of these respondents. No comorbid diseases were reported by 29.8% of children and by 11.7% of adults (p < 0.001). Conclusions: the results indicate that CD diagnosis is delayed in Poland, especially in adults, and clinicians should be aware of the diversity in CD presentation.

Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising Lactobacillus rhamnosus ŁOCK 0900, Lactobacillus rhamnosus ŁOCK 0908, and Lactobacillus casei ŁOCK 0918 in children under 2 years of age with AD and a cow’s milk protein (CMP) allergy. The study enrolled 151 children, who—apart from being treated with a CMP elimination diet—were randomized to receive the probiotic preparation at a daily dose of 109 bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant (p < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13–5.8; p = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85–19.67, p = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic ŁOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565).

The aim of this randomized double-blind placebo-controlled study was to evaluate the effectiveness and safety of multi-strain probiotic in adults with diarrhea-predominant irritable bowel syndrome (IBS-D). The patients were randomized to receive a mixture of Lactobacillus, Bifidobacterium, and Streptococcus thermophilus strains or placebo for eight weeks. Primary endpoints included changes in symptom severity and improvement assessed with the IBS Severity Scoring System (IBS-SSS) and Global Improvement Scale (IBS-GIS). The probiotic in comparison with placebo significantly improved the IBS symptom severity (the change of total IBS-SSS score from baseline −165.8 ± 78.9 in the probiotic group and −105.6 ± 60.2 in the placebo group, p = 0.005) and in the specific scores related to the severity of pain (p = 0.015) and the quality of life (p = 0.016) after eight weeks of intervention. The probiotic group indicated an improvement in symptoms with the use of the IBS-GIS compared with the placebo group after four (p = 0.04) and eight weeks (p = 0.003). The occurrence of adverse events did not differ between study groups. In conclusion, the multi-strain probiotic intervention resulted in a significant improvement in IBS symptoms evaluated with the use of both IBS-SSS and IBS-GIS scales. The results suggest that the studied probiotic preparation is well tolerated and safe and can offer benefits for patients with IBS-D. (registration number in Clinicaltrials.gov NCT 04662957).

The purpose of the randomized double-blind placebo-controlled trial was to assess the effectiveness of synbiotic preparation containing probiotic Lactobacillus rhamnosus FloraActive™ 19070-2, Lactobacillus acidophilus DSMZ 32418, Bifidobacterium lactis DSMZ 32269, Bifidobacterium longum DSMZ 32946, Bifidobacterium bifidum DSMZ 32403 and fructooligosaccharides in adult patients with diarrhea-dominant IBS (IBS-D). The study included eighty patients with moderate and severe IBS-D who were randomized to receive synbiotics or placebo for eight weeks. Finally, a total of sixty-eight patients finished the study. The primary endpoints included the assessment of the symptoms’ severity with IBS symptom severity scale (IBS-SSS), an improvement of IBS global symptoms with Global Improvement Scale (IBS-GIS) and adequate relief of symptoms after four and eight weeks of therapy. Secondary endpoints, which were collected by telephone interviewers three times a week included the assessment of individual IBS symptoms and adverse events. Synbiotic treatment in comparison to placebo significantly improved IBS-GIS (p = 0.043), and IBS-SSS score inducing a decrease in the total IBS-SSS (p = 0.042) and in domain-specific scores related to flatulence (p = 0.028) and bowel habit (p = 0.028) after four and eight weeks. Patients treated with synbiotics reported in weekly observations a significant amelioration in a feeling of incomplete bowel movements, flatulence, pain, stool pressure and diarrheal stools compared to those receiving placebo. There were no differences in adverse events between both groups. Concluding, the multi-strain synbiotic preparation was associated with a significant improvement in symptoms in IBS-D patients and was well-tolerated. These results suggest that the use of synbiotics offers a benefit for IBS-D patients. [Clinicaltrials.gov NCT04206410 registered 20 December 2019].

The increase in allergy prevalence observed in recent decades may be a consequence of early intestinal dysbiosis. The intestinal microbiota is formed in the first 1000 days of life, when it is particularly sensitive to various factors, such as the composition of the mother’s microbiota, type of delivery, infant’s diet, number of siblings, contact with animals, and antibiotic therapy. Breastfeeding and vaginal birth favorably affect the formation of an infant’s intestinal microbiota and protect against allergy development. The intestinal microbiota of these infants is characterized by an early dominance of Bifidobacterium, which may have a significant impact on the development of immune tolerance. Bifidobacterium breve is a species commonly isolated from the intestines of healthy breastfed infants and from human milk. This review outlines the most important environmental factors affecting microbiota formation and the importance of Bifidobacterium species (with a particular emphasis on Bifidobacterium breve) in microbiota modulation towards anti-allergic processes. In addition, we present the concept, which assumes that infant formulas containing specific probiotic Bifidobacterium breve strains and prebiotic oligosaccharides may be useful in allergy management in non-breastfed infants.

Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset.

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 (CD) is a lifelong condition and it often involves impaired nutrition, wide spectrum of symptoms and it requires constant dietetic treatment. The impact of the gluten-free diet on patients’ nutritional status and on the other biochemical parameters is being widely investigated. In this article we looked into particular risk factors that might lead to increased prevalence of atherosclerosis in CD patients, including nutritional status, gluten-free diet, lipids profile and concomitant disease—type 1 diabetes mellitus. Here, we present the current data and research on these risk factors of atherosclerosis with respect to celiac disease.

The aim of the study was to investigate the toxic effects of aflatoxin B1 (AFB1) and efficacy of a probiotic preparation containing L. reuteri, L. plantarum, L. pentosus, L. rhamnosus and L. paracasei and Saccharomyces cerevisiae yeasts to ameliorate their effects in broiler chickens. A total of 168 one-day-old female Ross 308 broilers were randomly allocated to six groups. Three wheat and soybean meal-based diets were prepared: Control diet and diets contaminated with 1 or 5 mg/kg AFB1 supplied in moldy wheat. All diets were unsupplemented or supplemented with probiotic, cold pelleted and fed from 1 to 35 day of life. Feeding diet with 1 mg AFB1/kg did not affect performance, but a diet with 5 mg AFB1 resulted in a significant reduction of feed intake and BWG, both diets induced liver and kidneys enlargement. The probiotic supplementation of the diets partially ameliorated those negative effects and resulted in a significant increase of AFB1 excretion. It was accompanied by the reduced level of AFB1 residues in the liver from 8.9 to 3.7 and from 11.8 to 5.9 µg/kg, in kidneys from 7.9 to 2.5 and from 13.7 to 4.1 µg/kg in birds fed the less and more contaminated diets, respectively. AFB1 exposure caused many severe histopathological changes in the liver and kidneys of broilers, probiotic supplementation significantly reduced the changes of these organs. It may be concluded that the probiotic supplementation can be used to alleviate the negative effects of contamination of broiler feed with AFB1 on bird health and product security.

The “microbiota hypothesis” ties the increase in allergy rates observed in highly developed countries over the last decades to disturbances in the gut microbiota. Gut microbiota formation depends on a number of factors and occurs over approximately 1000 days of life, including the prenatal period. During this period the microbiota helps establish the functional immune phenotype, including immune tolerance. The development of immune tolerance depends also on early exposure to potential food allergens, a process referred to as nutritional programming. This article elaborates on the concepts of microbial and nutritional programming and their role in the primary prevention of allergy.