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There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood., Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay., Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023., Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed., Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification)., Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Background & Aims: We studied the prevalence of functional abdominal pain disorders (FAPDs) and functional constipation (FC) in a large prospective cohort of children with celiac disease on a strict gluten-free diet (GFD)., Methods: We performed a prospective cohort study, from 2016 through 2018, in a tertiary care center in Italy, of 417 patients (37% male; mean age, 13.7 y) with a diagnosis of celiac disease (European Society for Paediatric Gastroenterology Hepatology, and Nutrition criteria) who had been on a strict GFD for more than 1 year and had negative results from serologic tests after being on the GFD. Parents and children (>10 y) were asked to fill in a questionnaire on pediatric gastrointestinal symptoms, according to Rome IV criteria. Patients' closest siblings (or cousins) who had negative results from serologic test for celiac disease were used as controls (n = 373; 39% male; mean age, 13.5 y)., Results: We found a higher prevalence of FAPDs among patients with celiac disease (11.5%) than controls (6.7%) (P < .05); the relative risk (RR) was 1.8 (95% CI, 1.1-3.0). Irritable bowel syndrome (IBS) and FC defined by the Rome IV criteria were more prevalent in patients with celiac disease (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively); the RR for IBS was 2.3 (95% CI, 1.1-4.6) and the RR for functional constipation was 2.1 (95% CI, 1.4-3.2). We found no differences in the prevalence of other subtypes of FAPDs. A logistic regression showed that younger age (P < .05) and a higher level of anti-transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration., Conclusions: Celiac disease is associated with an increased risk of IBS and FC. Strategies are needed to manage IBS and FC in patients with celiac disease., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years., Methods: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis., Results: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population., Conclusion: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.