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Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD is a unique autoimmune condition, as it is the only one in which the environmental trigger is known: gluten, a storage protein present in wheat, barley, and rye. How and when the loss of tolerance of the intestinal mucosa to gluten occurs is still unknown. This event, through the activation of adaptive immune responses, enhances epithelial cell death, increases the permeability of the epithelial barrier, and induces secretion of pro-inflammatory cytokines, resulting in the transition from genetic predisposition to the actual onset of the disease. While the role of gastrointestinal infections as a possible trigger has been considered on the basis of a possible mechanism of antigen mimicry, a more likely alternative mechanism appears to involve a complex disruption of the gastrointestinal microbiota ecosystem triggered by infections, rather than the specific effect of a single pathogen on intestinal mucosal homeostasis. Several lines of evidence show the existence of intestinal dysbiosis that precedes the onset of CeD in genetically at-risk subjects, characterized by the loss of protective bacterial elements that both epigenetically and functionally can influence the response of the intestinal epithelium leading to the loss of gluten tolerance. We have conducted a literature review in order to summarize the current knowledge about the complex and in part still unraveled dysbiosis that precedes and accompanies CeD and present some exciting new data on how this dysbiosis might be prevented and/or counteracted. The literature search was conducted on PubMed.gov in the time frame 2010 to March 2024 utilizing the terms "celiac disease and microbiota", "celiac disease and microbiome", and "celiac disease and probiotics" and restricting the search to the following article types: Clinical Trials, Meta-Analysis, Review, and Systematic Review. A total of 364 papers were identified and reviewed. The main conclusions of this review can be outlined as follows: (1) quantitative and qualitative changes in gut microbiota have been clearly documented in CeD patients; (2) intestinal microbiota's extensive and variable interactions with enterocytes, viral and bacterial pathogens and even gluten combine to impact the inflammatory immune response to gluten and the loss of gluten tolerance, ultimately affecting the pathogenesis, progression, and clinical expression of CeD; (3) gluten-free diet fails to restore the eubiosis of the digestive tract in CeD patients, and also negatively affects microbial homeostasis; (4) new tools allowing targeted microbiota therapy, such as the use of probiotics (a good example being precision probiotics like the novel strain of B. vulgatus (20220303-A2) begin to show exciting potential applications.

Inflammatory bowel diseases (IBD) are chronic, incurable inflammatory condition of the gut. They comprise Crohn's disease and ulcerative colitis. Crohn's disease (CD) may affect any tract of the gastrointestinal (GI) tract and is a transmural inflammatory condition; ulcerative colitis (UC), on the other hand, is limited to the mucosal layer of the rectum and colon. Treatment options available for both IBD are notoriously loaded with potentially serious side effects and risks. Although the pathogenesis of IBD involves a complex interaction between genetic, environmental, microbial and immunological factors, there is evidence that the interplay between the microbiota and the GI mucosa has a preponderant role. It is therefore no surprise that in recent years, a growing interest for effective and safer alternatives has focused on the potential role of prebiotics and-especially-probiotics.The mechanisms of action underlying the potential benefits of probiotics in IBD have been largely and quite extensively investigated in vitro and in vivo experiments. In terms of clinical evidence, the results of trials in the induction of remission of active CD or the maintenance of its remission with probiotics have been so far largely disappointing, to the point that their use in this disease cannot be at present recommended.On the contrary, for the treatment as well as for maintenance therapy of UC, there is clinical evidence of efficacy for some specific strains or multi-strain preparations.It is evident that this is a rapidly evolving and promising field; more data are very likely to yield a better understanding on what strains and in what doses should be used in different specific clinical settings, as we expect new and exciting developments of precision and even personalized therapy by the fast-growing field of probiogenomics., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: To gather the current evidence and to offer recommendations for follow-up and management., Methods: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%., Results: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care., Conclusions: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management., Competing Interests: Mearin received receipt of grants/research supports from Research Grant Eurospital, ThermoFisher and BioHit and served as member of advisory board and consultancy and speaker from ThermoFisher. Agardh received receipt of grants/research supports from Novo Nordisk Foundation and served as member of advisory board from Takeda and ThermoFischer. Antunes received receipt of payment/honorarium for lectures from Danone, Catassi received receipt of payment/honorarium for consultation from Dr Schar Food. Dolinsek received receipt of payment/honorarium for lectures from Medis, Abbot, Merit. Guandalini served as member of advisory board from ExeGIPharma, Imaware. Koletzko received receipt of grants/research supports from Mead-Johnson, Biogaia; served as member of advisory board from Abbvie, Danone, Jannsen, Sanofi, Takeda; receipt of payment/honorarium for lectures from Danone, Mead-Johnson, Nestlé Nutrition, Pfizer, Takeda; receipt of payment/honorarium for consultation from Danone. Korponay-Szabó other support from patent on celiac disease rapid test licensed to Labsystems Oy, Vantaa, Finland. Kurppa received receipt of grants/research supports from Finnish Pediatric Foundation, Päivikki, and Sakari Sohlberg Foundation; served as member of advisory board from Finnish Coeliac Society; receipt of payment/honorarium for lectures from Thermo Fisher; and receipt of payment/honorarium for consultation from Takeda. Rodriguez-Herrera received other support from Patent and detecting gluten peptides in human fluids, March 29, 2019—Universidad de Sevilla. Shamir received receipt of grants/research supports from Helmsley Foundation; served as member of advisory board: Nestle Nutrition Institute, Teva; receipt of payment/honorarium for lectures from Abbott, Nutricia, Nestle Nutrition Institute; receipt of payment/honorarium for consultation from Abbott, Else, Nutricia, Nestle Nutrition Institute and Stock shareholder from NGS. Ciacci received receipt of honoraria or consultation fees from Takeda, GSK, Mediserve, Biogen Celltrion. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Intestinal microbiota play a role in the health and performance of athletes, and can be influenced by probiotics. Thus, in this study, we aimed to investigate the effect of the use of probiotics combined with chronic exercise on the thiol/disulfide homeostasis, a novel marker of oxidative stress., Methods: Male Wistar rats were randomly divided into four groups: control (Cn), exercise (Ex), probiotics (P), and probiotics + exercise (PEx). A capsule containing 6 × 10 8 CFU of L. rhamnosus , L. paracasei, L. acidophilus, and B. lactis was given daily for eight weeks to all the experimental animals. The total thiol (TT, μmol/L) and native thiol (NT, μmol/L) concentrations were measured to determine the oxidative stress parameters. The dynamic disulfide (DD, %), reduced thiol (RT, %), oxidized thiol (OT, %), and thiol oxidation reduction (TOR, %) ratios were analyzed., Results: The TT level was found to be significantly higher in the Ex group (p = 0.047, η 2 = 0.259). The DD level, a marker of oxidation, was significantly lower in the PEx group (p = 0.042, η 2 = 0.266); the highest value of this parameter was found in the Ex group. The use of probiotics alone had no effect on thiol/disulfide homeostasis., Conclusions: We showed, for the first time, that probiotics administered "with exercise" decreased dynamic disulfide and significantly reduced oxidative damage. Therefore, we speculate that the use of probiotics in sports involving intense exercise might be beneficial to reduce oxidative stress.

Purpose: To evaluate changes in peripapillary vascular blood flow indices (PVBFI) in patients with thyroid-associated ophthalmopathy (TAO) using OCT angiography (OCTA) technology., Methods: Patients with TAO and control subjects matched for age and sex were included in the study. Eye examination, Clinical Activity Score (CAS) evaluation and OCTA scan analysis (Topcon ImageNet 6; DRI OCT Triton, Topcon Corporation) were performed. In particular, PVBFI of the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR) and choriocapillaris (CC) layers were obtained by OCTA and extracted from 8-bit greyscale OCT images using the ImageJ software package., Results: Twenty-six patients with TAO (19 females, mean age 54.7 ± 5.2 and 7 males, mean age 51.4 ± 16.3) were compared with 26 healthy subjects (15 females, mean age 48.2 ± 14.1 and 11 males, mean age 53.1 ± 15.2). Both DCP-PVBF and CC-PVBFI were significantly reduced in TAO patients compared to control eyes (28.6 ± 2.1 vs. 29.7 ± 0.93, p = 0.002; 46.5 ± 1.72 vs. 47.2 ± 1.2, p = 0.019 respectively); on the other hand, no statistically significant differences were found in SCP-PVBFI and OR-PVBFI in TAO patients compared to healthy subjects (p > 0.05). Also, CC-PVBFI was associated with elevated values of CAS (p = 0.018) and ROC curve showed that patients with elevated CC-PVBFI were correlated with active TAO (CAS > 3) (p = 0.012)., Conclusions: TAO disease may be associated with changes in DCP-PVBFI and CC-PVBFI; also, CC-PVBFI seems to correlate with disease activity., (© 2022. The Author(s).)

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Assessment and management of pain are essential components of pediatric care. Pain in pediatric age is characterized by relevant health and socio-economic consequences due to parental concern, medicalization, and long-term physical and psychological impact in children. Pathophysiological mechanisms of nociception include several pathways in which also individual perception and gut-brain axis seem to be involved. In this narrative review, we analyze the rational and the current clinical findings of probiotic use in the management of functional gastrointestinal disorders (FGID) in pediatric age, with special focus on infantile colic, irritable bowel syndrome, constipation, and gastroesophageal reflux. Some specific probiotics showed a significant reduction in crying and fussing compared to placebo in breastfed infants with colic, although their exact mechanism of action in this disorder remains poorly understood. In irritable bowel syndrome, a limited number of studies showed that specific strains of probiotics can improve abdominal pain/discomfort and bloating/gassiness, although data are still scarce. As for constipation, whilst some strains appear to reduce the number of hard stools in constipated children, the evidence is not adequate to support the use of probiotics in the management of functional constipation. Similarly, although some probiotic strains could promote gastric emptying with a potential improvement of functional symptoms related to gastroesophageal reflux, current evidence is insufficient to provide any specific recommendation for the prevention or treatment of gastroesophageal reflux. In conclusion, probiotics have been proposed as part of management of pain in functional gastrointestinal disorders in pediatric age, but mechanisms are still poorly understood and evidence to guide clinical practice is currently inadequate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Capozza, Laforgia, Rizzo, Salvatore, Guandalini and Baldassarre.)