Risk Of Celiac Disease Research Articles

Predominantly antibody deficiency and the association with celiac disease in Sweden: A nationwide case-control study

BackgroundPredominantly antibody deficiency (PAD) is associated with noninfectious inflammatory gastrointestinal disease. Population estimates of celiac disease (CeD) risk in those with PAD are limited. ObjectiveTo estimate population risk of PAD in individuals with CeD. MethodsWe conducted a nationwide case-control study in Swedish individuals who received a diagnosis of CeD between 1997 and 2017 (n = 34,980), matched to population comparators by age, sex, calendar year, and county. The CeD was confirmed through the Epidemiology Strengthened by histopathology Reports in Sweden study, which provided information on biopsy specimens from each of Sweden's pathology departments. PAD was identified using International Classification of Diseases, 10th Revision coding and categorized according to the International Union of Immunologic Societies. Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% CIs. ResultsPAD was more prevalent in CeD than in population controls (n = 105 [0.3%] vs n = 57 [0.033%], respectively). This translated to an aOR of 8.23 (95% CI 5.95-11.48). The association was strongest with common variable immunodeficiency (aOR 17.25; 95% CI 6.86-52.40), and slightly lower in other PAD (aOR 8.39; 95% CI 5.79-12.32). The risk of CeD remained increased at least 5 years after diagnosis of PAD (aOR 4.79; 95% CI 2.89-7.97, P-heterogeneity ≤ 0.001). ConclusionPAD was associated with an increased risk of CeD. A particularly strong association was seen in those with CVID, although this should be interpreted cautiously given the limited understanding of the mechanisms of histopathologic changes in these patients.

Evaluating the Effects of Chronic Oral Exposure to the Food Additive Silicon Dioxide on Oral Tolerance Induction and Food Sensitivities in Mice.

The increasing prevalence of food sensitivities has been attributed to changes in gut microenvironment; however, ubiquitous environmental triggers such as inorganic nanoparticles (NPs) used as food additives have not been thoroughly investigated. We explored the impact of the NP-structured food-grade silicon dioxide () on intestinal immune response involved in oral tolerance (OT) induction and evaluated the consequences of oral chronic exposure to this food-additive using a mouse model of OT to ovalbumin (OVA) and on gluten immunopathology in mice expressing the celiac disease risk gene, HLA-DQ8. Viability, proliferation, and cytokine production of mesenteric lymph node (MLN) cells were evaluated after exposure to . C57BL/6J mice and a mouse model of OT to OVA were orally exposed to or vehicle for 60 d. Fecal lipocalin-2 (Lcn-2), anti-OVA IgG, cytokine production, and immune cell populations were analyzed. Nonobese diabetic (NOD) mice expressing HLA-DQ8 (NOD/DQ8), exposed to or vehicle, were immunized with gluten and immunopathology was investigated. MLN cells exposed to presented less proliferative T cells and lower secretion of interleukin 10 (IL-10) and transforming growth factor beta () by T regulatory and cells compared to control, two factors mediating OT. Mice given exhibited intestinal Lcn-2 level and interferon gamma () secretion, showing inflammation and less production of IL-10 and . These effects were also observed in OVA-tolerized mice exposed to , in addition to a breakdown of OT and a lower intestinal frequency of T cells. In NOD/DQ8 mice immunized with gluten, the villus-to-crypt ratio was decreased while the intraepithelial lymphocyte counts and the Th1 inflammatory response were aggravated after treatment. Our results suggest that chronic oral exposure to blocked oral tolerance induction to OVA, and worsened gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between exposure and food sensitivities in humans. https://doi.org/10.1289/EHP12758.

Investigating the role of iron status in the development of coeliac disease: a Mendelian randomisation study

ObjectiveThe environmental trigger behind the increasing prevalence of coeliac disease is not known. One suggested cause is iron deficiency, which is common in coeliac disease. We aimed to evaluate this...

1013 Preterm delivery and the risk for childhood celiac disease of the offspring

1013 Preterm delivery and the risk for childhood celiac disease of the offspring

739 Maternal fertility treatments and the risk for celiac disease of the offspring

739 Maternal fertility treatments and the risk for celiac disease of the offspring

Associação dos alelos de risco HLA-DQ2 e HLA-DQ8 à lesão intestinal e sorologia em pacientes com doença celíaca

ABSTRACT Objective This study aims to describe the distribution of main celiac disease risk alleles related to human leucocyte antigen complex and their association to the severity of intestinal injury, serological test results, CD-associated diseases and symptomatology. Methods The DNA of 140 celiac disease patients was analyzed, and the distribution of the three most important risk alleles to the celiac disease development was identified (DQA1*05:01, DQB1*02:01 and DRB1*04, the last one as a DQB1*03:02/DQA1*03/DRB1*04 haplotype marker). Data on serological tests, biopsy results, symptomatology and incidence of CD-associated diseases were collected by using a previously validated questionnaire. Results It was found that 98% of patients presented at least one copy of the studied alleles. Patients carrying simultaneously both HLA-DQ2 risk alleles were highly prevalent (75%), and 20.7% patients carried the HLA-DQ8 haplotype. Positive patients for both HLA-DQ2 risk alleles presented positive association to anti-gliadin (p=0.037), anti-endomysium (p=0.001) and anti-transglutaminase (p=0.032) serological tests, and a higher prevalence of osteoporosis and hypothyroidism. Patients carrying one or none of those alleles often presented negative serological results. In addition, it was found an association between intestinal injury severity and genetic profile (No-BreakpNo-Break<0.001). Conclusion Results suggest that the HLA-DQ genotyping are associated to serological tests and the severity of intestinal damage in celiac disease patients.

Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach.

Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide-HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89-94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.

Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood.

Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D. We genotyped 373 controls and 384 children who developed CD or T1D in the population-based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen(HLA)-DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non-HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype. HLA genotypes for CD and T1D or non-HLA GRS for T1D were not associated with infections. The non-HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95%CI: 0.87-1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81-0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95%CI: 0.83-1.01).SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non-HLA GRS (OR: 1.24). HLA variants and non-HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies.

Phenome-wide association study on miRNA-related sequence variants: the UK Biobank

BackgroundGenetic variants in the coding region could directly affect the structure and expression levels of genes and proteins. However, the importance of variants in the non-coding region, such as microRNAs (miRNAs), remain to be elucidated. Genetic variants in miRNA-related sequences could affect their biogenesis or functionality and ultimately affect disease risk. Yet, their implications and pleiotropic effects on many clinical conditions remain unknown.MethodsHere, we utilised genotyping and hospital records data in the UK Biobank (N = 423,419) to investigate associations between 346 genetic variants in miRNA-related sequences and a wide range of clinical diagnoses through phenome-wide association studies. Further, we tested whether changes in blood miRNA expression levels could affect disease risk through colocalisation and Mendelian randomisation analysis.ResultsWe identified 122 associations for six variants in the seed region of miRNAs, nine variants in the mature region of miRNAs, and 27 variants in the precursor miRNAs. These included associations with hypertension, dyslipidaemia, immune-related disorders, and others. Nineteen miRNAs were associated with multiple diagnoses, with six of them associated with multiple disease categories. The strongest association was reported between rs4285314 in the precursor of miR-3135b and celiac disease risk (odds ratio (OR) per effect allele increase = 0.37, P = 1.8 × 10–162). Colocalisation and Mendelian randomisation analysis highlighted potential causal role of miR-6891-3p in dyslipidaemia.ConclusionsOur study demonstrates the pleiotropic effect of miRNAs and offers insights to their possible clinical importance.

Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk

BackgroundHigher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence. ObjectivesThis study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children. MethodsData was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake. ResultsAt age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03). ConclusionsDietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.

Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

Genetic variation in environmental enteropathy and stunting in Zambian children: A pilot genome wide association study using the H3Africa chip.

Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy. Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array. Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at P<5x10-8, likely due to the small sample size, interesting associations were observed at lower thresholds. SNPs associated with stunting were in genomic regions known to modulate neuronal differentiation and fatty acid biosynthesis. SNPs associated with increased microbial translocation were associated with non-integrin membrane ECM interactions, tight junctions, hemostasis, and G-alpha signalling events. SNPs associated with increased inflammation were associated with, ECM interactions, purine metabolism, axon guidance, and cell motility. SNPs negatively associated with inflammation overlapped genes involved in semaphoring interactions. We explored the existing coeliac disease risk HLA genotypes and found present: DQ2.5 (7.5%), DQ8 (3.5%) and DQ2.2 (3.8%); however, no children were positive for coeliac antibodies. We detected HLA-DRB:1301 and HLA-C:1802 with high odds ratios and P<0.05 in stunted children compared to controls. Genetic variations associated with stunting and the enteropathy underlying it, include variants associated with multiple pathways relating to gene expression, glycosylation, nerve signalling, and sensing of the nutritional and microbiological milieu.

A review of the long-term use of proton pump inhibitors and risk of celiac disease in the context of HLA-DQ2 and HLA-DQ8 genetic predisposition.

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.

Increased Risk of Celiac Disease in Patients with Uveitis

ABSTRACT Purpose To examine whether patients with non-infectious uveitis (NIU) are at increased risk for celiac disease (CeD). Methods Celiac antibody testing was completed in 112 patients. The control group included patients who had undergone upper endoscopy for suspicion of CeD. Results 2/112 (1.79%) of patients with NIU had positive anti-tTG serology and CeD was confirmed in both patients. When compared to the expected risk of CeD in the general Israeli population of 0.31%, this corresponded to an odds ratio of 5.77 (95% CI 1.4118 to 23.4737, P = 0.049). Three additional patients had positive serology for CeD but the diagnosis was not confirmed. Conclusions An increased risk of CeD was detected in patients with NIU. We therefore recommend screening for CeD in NIU patients. Larger prospective studies are required to further validate these results.

Autoimmune gastritis as an unexpected cause of diarrhea in a young adult with type I diabetes: a case report

BackgroundType 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.Case presentationA 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient’s initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.ConclusionThis case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.

Celiac disease in paediatric patients in the United Arab Emirates: a single-center descriptive study.

Celiac disease (CD) is an autoimmune disorder that is provoked by the consumption of gluten in genetically vulnerable individuals. CD affects individuals worldwide with an estimated prevalence of 1% and can manifest at any age. Growth retardation and anemia are common presentations in children with CD. The objective of this study is to estimate the prevalence of CD in multiple "at risk groups" and to characterize children with CD, presented to a tertiary hospital in Dubai, United Arab Emirates (UAE). The study reviewed medical charts of all patients <18 years who had received serologic testing for CD. The study was conducted at Al Jalila Children's Specialty Hospital in Dubai, UAE, from January 2018 to July 2021. Extracted information from medical records included sociodemographics, laboratory findings, clinical presentation, and any associated co-morbidities. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria were used to identify patients with CD. During the study period, 851 paediatric patients underwent serological screening for CD, out of which, 23 (2.7%) were confirmed with CD. Of the 23 patients diagnosed with CD, 43.5% had no gastrointestinal symptoms. Diabetes type 1 (30.4%) followed by iron deficiency anaemia (30%) and Hashimoto thyroiditis (9%) were the most commonly associated comorbidities. The prevalence of CD among paediatric patients with autoimmune thyroiditis (12.5%) was 1.92-times higher than that among paediatric patients with diabetes type 1 (6.5%). The results of this study show that almost three out of every 100 paediatric patients who were screened for CD were confirmed to have the condition. These findings highlight the importance of screening children who are at risk or present symptoms suggestive of CD, to ensure early diagnosis and appropriate management.

The Combined Effect of Infant and Mother Secretor Status on Infant Susceptibility to Viral Gastroenteritis and Celiac Disease

Celiac disease is a prevalent autoimmune disorder with a rising incidence of 7.5% annually during the second half of the 20&lt;sup&gt;th&lt;/sup&gt; century and the 21&lt;sup&gt;st&lt;/sup&gt; century. Not all genetically susceptible individuals that carry the risk alleles HLA DQ2 and DQ8 go on to develop celiac disease, suggesting that there may be other environmental triggers that contribute to the development of celiac disease in genetically susceptible individuals. Gastroenteritis during infancy has been shown to be associated with increased risk of celiac disease. Secretor status, per the FUT2 genotype, and subsequent alterations in the microbiota, is associated with risk of gastroenteritis in infants. This review investigates the literature from January 2010 to June 2022 to determine the combined effect of secretor status and viral gastroenteritis on the development of celiac disease.&lt;strong&gt; &lt;/strong&gt;Mothers with the secretor phenotype and infants with the non-secretor phenotype provided the most protection against particular strains of gastroenteritis and celiac disease. Both the maternal and infant secretor status, as well as the infant’s Lewis status and ABO blood group can influence the infant’s susceptibility to different viral strains, which cause gastroenteritis. Gastroenteritis caused by viral infections can damage intestinal epithelial cells, cause dysbiosis, and affect pro-inflammatory cytokines, which exacerbate celiac disease onset. Understanding the effect of secretor status and gastroenteritis on celiac disease may provide a novel approach to early screening and preventative strategies to reduce risk factors that contribute to the onset of celiac disease.

Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease-A Narrative Review.

Celiac disease (CD) is a multifactorial disorder, defined by a complex interplay of genetic and environmental factors. Both genetic predisposition and dietary exposure to gluten are essential factors in triggering CD. However, there is proof that their presence is necessary, but not sufficient, for disease development. Through gut microbiota modulation, several additional environmental factors have shown their potential role as co-factors in CD pathogenesis. The aim of this review is to illustrate the possible mechanisms that stand behind the gut microbiota's involvement in CD pathogenesis. Furthermore, we discuss microbiota manipulation's potential role as both a preventative and therapeutic option. The available literature provides evidence that even before CD onset, factors including cesarean birth and formula feeding, as well as intestinal infection exposure, amplify the risk of CD in genetically predisposed individuals, due to their influence on the intestinal microbiome composition. Active CD was associated with elevated levels of several Gram-negative bacterial genera, including Bacteroides, Escherichia, and Prevotella, while beneficial bacteria such as lactobacilli and bifidobacteria were less abundant. Viral and fungal dysbiosis has also been described in CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve the clinical symptoms and duodenal histopathology, but the persistence of intestinal dysbiosis in CD children under a GFD urges the need for additional therapy. Probiotics, prebiotics, and fecal microbial transplant have demonstrated their efficacy in restoring gut microbiota eubiosis in adult CD patients; however, their efficacy and safety as adjunctive therapies to a GFD in pediatric patients needs further investigation.

The risk for celiac disease after Covid-19 infection

BackgroundCeliac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.Patients and methodsAll patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.ResultsDuring the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75).ConclusionsOur results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Assessment of causal associations among gut microbiota, metabolites, and celiac disease: a bidirectional Mendelian randomization study.

A growing number of studies have implicated that gut microbial abundance and metabolite concentration alterations are associated with celiac disease (CD). However, the causal relationship underlying these associations is unclear. Here, we used Mendelian randomization (MR) to reveal the causal effect of gut microbiota and metabolites on CD. Genome-wide association study (GWAS) summary-level data for gut microbiota, metabolites, and CD were extracted from published GWASs. Causal bacterial taxa and metabolites for CD were determined by two-sample MR analyses. The robustness of the results was assessed with sensitivity analyses. Finally, reverse causality was investigated with a reverse MR analysis. Genetically, increased genus Bifidobacterium was potentially associated with higher CD risk (odds ratio [OR] = 1.447, 95% confidence interval [CI]: 1.054-1.988, p = 0.022) while phylum Lentisphaerae (OR = 0.798, 95% CI: 0.648-0.983, p = 0.034) and genus Coprobacter (OR = 0.683, 95% CI: 0.531-0.880, p = 0.003) were related to lower CD risk. Moreover, there were suggestive associations between CD and the following seven metabolites: 1-oleoylglycerophosphoethanolamine, 1-palmitoylglycerophosphoethanolamine, 1,6-anhydroglucose, phenylacetylglutamine, tryptophan betaine, 10-undecenoate, and tyrosine. Sensitivity analyses deemed the results reliable without pleiotropy. We investigated the causal relationships between gut microbiota, metabolites, and CD with two-sample MR. Our findings suggest several novel potential therapeutic targets for CD treatment. Further understanding of the underlying mechanism may provide insights into CD pathogenesis.