Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing.

Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten.

While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Celiac disease (CeD) is an immune-mediated condition that occurs in genetically predisposed individuals ingesting gluten. It is characterized by enteropathy leading to both gastrointestinal and extra-intestinal symptoms. The prevalence of CeD has increased world-wide. Evidence suggests that genetic predisposition and exposure to gluten are necessary but not sufficient for CeD onset, implying that other unknown factors are at play in its pathogenesis.

This review summarizes the current knowledge on the contribution of the gut microbiota to CeD pathogenesis, aiming to address the question of whether it is the cause or consequence of the celiac enteropathy. We reviewed the current literature (studies published in PubMed database between 2007 and 2023), linking gut microbiota dysbiosis and CeD, focusing specifically on prospective birth cohorts' studies and discussing how multi-omics and artificial intelligence (AI) could transform the diagnosis of CeD in a personalized medicine approach.

A multi-omic approach will allow for better clarification of the pivotal role of the microbiome in epigenetically triggering CeD pathogenesis. Further, the combination of multi-omics results with AI would pave the way to an improved CeD diagnosis and to the identification of new personalized therapeutic interventions.

The gut barrier encompasses several interactive, physical, and functional components, such as the gut microbiota, the mucus layer, the epithelial layer and the gut mucosal immunity. All these contribute to homeostasis in a well-regulated manner. Nevertheless, this frail balance might be disrupted for instance by westernized dietary habits, infections, pollution or exposure to antibiotics, thus diminishing protective immunity and leading to the onset of chronic diseases. Several gaps of knowledge still exist as regards this multi-level interaction. In this review we aim to summarize current evidence linking food antigens, microbiota and gut permeability interference in diverse disease conditions such as celiac disease (CeD), non-celiac wheat sensitivity (NCWS), food allergies (FA), eosinophilic gastrointestinal disorder (EOGID) and irritable bowel syndrome (IBS). Specific food elimination diets are recommended for CeD, NCWS, FA and in some cases for EOGID. Undoubtfully, each of these conditions is very different and quite unique, albeit food antigens/compounds, intestinal permeability and specific microbiota signatures orchestrate immune response and decide clinical outcomes for all of them.

Preterm infants are at an increased risk of developing feeding intolerance (FI) due to the functional immaturity of their gastrointestinal tract. Recent studies and meta-analyses have shown a significant role of bovine lactoferrin (LF) in the management of feeding intolerance and sepsis. This study aimed to assess the effects of oral bovine LF supplementation on FI in preterm infants (26-34 weeks gestational age) and its effect on intestinal permeability measured by serum zonulin concentrations.

A randomized controlled double-blind interventional pilot study was conducted in the Neonatal Intensive Care Unit (NICU) of Mansoura University. Sixty preterm neonates with FI were included in the study and were randomly assigned into two groups: lactoferrin group (100 mg/day bovine LF for 4 weeks or until discharge) and control group.

The time needed to achieve full enteral feeding of sixty preterm infants (26-34 weeks gestational age) (9 vs. 15 days, P = 0.001) was significantly shorter and serum zonulin concentrations at end of the trial or discharge (3.38 vs. 5.49 ng/ml, P = 0.04) were significantly lower in the lactoferrin group compared with the control group.

Oral bovine lactoferrin given to preterm infants (26-34 weeks gestational age) is associated with improvement of feeding intolerance and decreased intestinal permeability.

This study was registered at clinical trials.gov with ID (NCT04738058) at 2 March 2021.

Celiac disease (CD) is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals, leading to intestinal inflammation and damage. This chronic disease affects approximately 1% of the world's population and is a growing health challenge due to its increasing prevalence. The development of CD is a complex interaction between genetic predispositions and environmental factors, especially gluten, culminating in a dysregulated immune response. The only effective treatment at present is a strict, lifelong gluten-free diet. However, adherence to this diet is challenging and often incomplete, so research into alternative therapies has intensified. Recent advances in understanding the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effective and manageable treatment options. This review examines the latest innovations in CD therapies. The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis. We discuss both quantitative strategies such as enzymatic degradation of gluten, and qualitative approaches including immunomodulation and induction of gluten tolerance. Innovative treatments currently under investigation include transglutaminase inhibitors, which prevent the modification of gluten peptides, and nanoparticle-based therapies to recalibrate the immune response. These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions. The integration of these new therapies could revolutionize the treatment of CD and shift the paradigm from strict dietary restrictions to a more flexible and patient-friendly therapeutic approach. This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collaboration to integrate these advances into standard clinical practice.

In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non-invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix.

To conduct a systematic literature search and summarize the existing evidence for host mucosa-derived faecal biomarkers in evaluating small intestinal damage.

We searched for studies on PubMed (MEDLINE) until 1 March 2024.

We identified 494 studies and included 35 original case-control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell-mediated, innate and gluten-induced immune responses. In coeliac disease, faecal calprotectin and anti-gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β-defensin-2, lipocalin-2, zonulin-related proteins and angiotensin-converting enzyme. In environmental enteropathy, a non-significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet-derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy.

Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

Studies have indicated an association between cesarean section (CS), especially elective CS, and an increased risk of celiac disease (CD), but the conclusions of other studies are contradictory. The primary aim of this study (CD-deliver-IT) was to evaluate the rate of CS in a large population of CD patients throughout Italy.  METHODS: This national multicenter retrospective study was conducted between December 2020 and November 2021. The coordinating center was the Pediatric Gastroenterology and Liver Unit of Policlinico Umberto I, Sapienza, University of Rome, Lazio, Italy. Eleven other referral centers for CD have participated to the study. Each center has collected data on mode of delivery and perinatal period of all CD patients referring to the center in the last 40 years.

Out of 3,259 CD patients recruited in different Italian regions, data on the mode of delivery were obtained from 3,234. One thousand nine hundred forty-one (1,941) patients (60%) were born vaginally and 1,293 (40%) by CS (8.3% emergency CS, 30.1% planned CS, 1.5% undefined CS). A statistically significant difference was found comparing median age at time of CD diagnosis of patients who were born by emergency CS (4 years, CI 95% 3.40-4.59), planned CS (7 years, CI 95% 6.02-7.97) and vaginal delivery (6 years, CI 95% 5.62-6.37) (log rank p < 0.0001).

This is the first Italian multicenter study aiming at evaluating the rate of CS in a large population of CD patients through Italy. The CS rate found in our CD patients is higher than rates reported in the general population over the last 40 years and emergency CS seems to be associated with an earlier onset of CD compared to vaginal delivery or elective CS in our large nationwide retrospective cohort. This suggests a potential role of the mode of delivery on the risk of developing CD and on its age of onset, but it is more likely that it works in concert with other perinatal factors. Further prospective studies on other perinatal factors potentially influencing gut microbiota are awaited in order to address heavy conflicting evidence reaming in this research field.

Celiac disease (CeD) is a chronic autoimmune condition driven by gluten ingestion in genetically predisposed individuals, resulting in inflammatory lesions in the proximal small intestine. Although the presence of specific HLA-linked haplotypes and gluten consumption are necessary for disease development, they alone do not account for the variable onset of CeD in susceptible individuals. This review explores the multifaceted role of non-host factors in CeD development, including dietary and microbial influences. We discuss clinical associations and observations highlighting the impact of these factors on disease onset and severity. Furthermore, we discuss studies in CeD-relevant animal models that offer mechanistic insights into how diet, the microbiome, and enteric infections modulate CeD pathogenesis. Finally, we address the clinical implications and therapeutic potential of understanding these cofactors offering a promising avenue for preventive and therapeutic interventions in CeD management.

Celiac disease, an autoimmune disorder induced by the ingestion of gluten, affects approximately 1.4% of the population. Gluten damages the villi of the small intestine, producing symptoms such as abdominal pain, bloating and a subsequent loss of nutrient absorption, causing destabilization of the nutritional status. Moreover, gluten can trigger extra intestinal symptoms, such as asthma or dermatitis, but also mental disorders such as depression or anxiety. Moreover, people suffering from celiac disease sometimes feel misunderstood by society, mainly due to the lack of knowledge about the disease and the gluten-free diet. Thus, the treatment and follow-up of patients with celiac disease should be approached from different perspectives, such as the following: (1) a clinical perspective: symptomatology and dietary adherence monitorization; (2) nutritional assessment: dietary balance achievement; (3) psychological assistance: mental disorders avoidance; and (4) social inclusion: educating society about celiac disease in order to avoid isolation of those with celiac disease. The aim of this narrative review is to gain deep insight into the different strategies that currently exist in order to work on each of these perspectives and to clarify how the complete approach of celiac disease follow-up should be undertaken so that the optimum quality of life of this collective is reached.

Celiac disease (CD) is a chronic immune-mediated inflammatory disease of the small intestine caused by aberrant immune responses to consumed gluten proteins. CD is diagnosed by a combination of the patients reported symptoms, serologic and endoscopic biopsy evaluation of the small intestine; and adherence to a strict gluten-free diet (GFD) is considered the only available therapeutic approach for this disorder. Novel approaches need to be considered for finding new biomarkers to help this disorder diagnosis and finding a new alternative therapeutic method for this group of patients. Metabolomics and lipidomics are powerful tools to provide highly accurate and sensitive biomarkers. Previous studies indicated a metabolic fingerprint for CD deriving from alterations in gut microflora or intestinal permeability, malabsorption, and energy metabolism. Moreover, since CD is characterized by increased intestinal permeability and due to the importance of membrane lipid components in controlling barrier integrity, conducting lipidomics studies in this disorder is of great importance. In the current study, we tried to provide a critical overview of metabolomic and lipidomic changes in CD.

Here, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect. Challenges in implementation underscore the need for advanced technologies, scientific transparency, and public engagement. Future perspectives advocate for understanding maternal-neonatal microbiome, exploring the maternal exposome and delving into human milk's role in the establishment and restoration of the infant microbiome and its influence over health and disease. An integrated scientific approach, employing multi-omics and accounting for inter-individual variance in microbiome composition and function appears central to unleash the full potential of early-life microbiome interventions in revolutionizing healthcare.