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Nutrients Dec 2021Gluten-induced T-cell-mediated immune response damages the villous structure that significantly affects the functioning of the small intestinal mucosa [...].
Gluten-induced T-cell-mediated immune response damages the villous structure that significantly affects the functioning of the small intestinal mucosa [...].
Topics: Celiac Disease; Diet, Gluten-Free; Humans; Malnutrition; Thyroid Diseases
PubMed: 34960029
DOI: 10.3390/nu13124476 -
Frontiers in Immunology 2023Common Variable Immunodeficiency (CVID), a complex primary immunodeficiency syndrome defined by defective B cell responses to infection and vaccination, has...
Common Variable Immunodeficiency (CVID), a complex primary immunodeficiency syndrome defined by defective B cell responses to infection and vaccination, has heterogeneous clinical manifestations. Gastrointestinal (GI) complications in CVID, both infectious and non-infectious, can cause significant impairment leading to malabsorption and frank malnutrition. In order to better characterize the spectrum of GI disease associated with CVID, we describe 114 patients with GI disease (15.6%) from our 728 patient single center CVID cohort. Norovirus, Giardia and Cytomegalovirus were the most frequently isolated infectious pathogens. CVID enteropathy was the most encountered GI diagnosis based on endoscopy, with only a minority of patients having Crohn's disease (6.1%) or ulcerative colitis/proctitis (4.5%). Concurrent autoimmunity (30.7%), lung disease (18.4%) and malignancy (8.7%) were also present in significant proportion of subjects. Lastly, 16 of 47 (34%) who underwent whole exome sequencing demonstrated a culprit gene defect associated with CVID.
Topics: Humans; Common Variable Immunodeficiency; Malabsorption Syndromes; Crohn Disease; Colitis, Ulcerative; Autoimmunity
PubMed: 37711607
DOI: 10.3389/fimmu.2023.1209570 -
Clinical Nutrition ESPEN Oct 2023Symptoms of the disorders across the irritable bowel syndrome (IBS) spectrum include several different, usually postprandial, abdominal complaints. Up to date, dietary... (Review)
Review
Symptoms of the disorders across the irritable bowel syndrome (IBS) spectrum include several different, usually postprandial, abdominal complaints. Up to date, dietary treatments of the IBS have neither been personalized nor diagnosed with sufficient scientific evidence. They have mostly been treated using 'one-size-fits-all' approaches. Such include exclusion diets, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and gluten-free diets, lactose-free diets, a diet recommended by the UK National Institute for Health and Care Excellence, and a wheat-free diet. The exact pathophysiology of IBS disorders across the spectrum is still unclear. However, the symptom profile of IBS spectrum disorders seems similar to that of food intolerance/malabsorption syndromes. Celiac disease, fructose malabsorption, histamine intolerance and lactose intolerance represent food intolerance/malabsorption disorders based on the indigestion of sugars and/or proteins. Helicobacter pylori infection may potentially promote the development of IBS and, when facing a case of IBS-like symptoms, a search for intolerance/malabsorption and H. pylori should be added to find the correct treatment for the respective patient. This review will discuss why the 'one-size-fits-all' dietary approach in the treatment of complaints across the IBS spectrum cannot be successful. Hence, it will provide an overview of the most common overall dietary approaches currently used, and why those should be discouraged. Alternatively, a noninvasive diagnostic workup of the pathophysiologic factors of food intolerance/malabsorption in each patient with symptoms of the IBS spectrum is suggested. Additionally, if H. pylori is found, eradication therapy is mandatory, and if food intolerance/malabsorption is detected, an individual and personalized dietary intervention by a registered dietician is recommended.
Topics: Humans; Irritable Bowel Syndrome; Food Intolerance; Helicobacter Infections; Helicobacter pylori; Malabsorption Syndromes
PubMed: 37739739
DOI: 10.1016/j.clnesp.2023.06.028 -
American Journal of Physiology.... Aug 2019The prevalence of celiac disease (CeD) has increased in the last decades, suggesting a role for environmental factors in addition to gluten. Several cohort studies have... (Review)
Review
The prevalence of celiac disease (CeD) has increased in the last decades, suggesting a role for environmental factors in addition to gluten. Several cohort studies have shown that different gastrointestinal infections increase CeD risk. However, the mechanisms by which microbes participate in CeD have remained elusive. Recently, with the use of animal models, both viral and bacterial opportunistic pathogens were shown to induce immune activation relevant for CeD. The hypothesis that viral and/or bacterial infections can contribute to immune activation and breakdown of tolerance toward gluten in genetically susceptible individuals is therefore reinforced. Here, we discuss the evidence regarding the role of microbes in promoting CeD and the specific pathways triggered by microbes that could participate in CeD pathogenesis. Understanding these pathways will allow us to develop optimal microbiota-modulating strategies to help prevent CeD.
Topics: Bacterial Infections; Celiac Disease; Gastrointestinal Microbiome; Glutens; Humans; Immune Tolerance
PubMed: 31188640
DOI: 10.1152/ajpgi.00099.2019 -
Digestive Diseases and Sciences Jun 2021It is not known if genetic background, characteristics at diagnosis, physical and psychological well-being, and adherence to a gluten-free diet are comparable between... (Comparative Study)
Comparative Study
BACKGROUND
It is not known if genetic background, characteristics at diagnosis, physical and psychological well-being, and adherence to a gluten-free diet are comparable between patients with familial or sporadic celiac disease. These issues were investigated in a follow-up study.
METHODS
Altogether 1064 patients were analyzed for celiac disease-associated serology, predisposing HLA-DQ, and non-HLA genotypes. Medical data were collected from patient records and supplementary interviews. Current symptoms and quality of life were further evaluated with the Gastrointestinal Symptom Rating Scale (GSRS), the Psychological General Well-Being questionnaire (PGWB), and Short Form 36 (SF-36) questionnaires.
RESULTS
Familial and sporadic groups differed (P < 0.001) in the reason for diagnosis and clinical presentation at diagnosis, familial patients being more often screen-detected (26% vs. 2%, P < 0.001) and having less often gastrointestinal (49% vs. 69%) and severe symptoms (47% vs. 65%). The groups were comparable in terms of histological damage, frequency of malabsorption, comorbidities, childhood diagnoses, and short-term treatment response. At the time of the study, familial cases reported fewer symptoms (21% vs. 30%, P = 0.004) and lower prevalence of all (78% vs. 86%, P = 0.007), neurological (10% vs. 15%, P = 0.013), and dermatological (9% vs. 17%, P = 0.001) comorbidities. Dietary adherence and GSRS scores were comparable, but familial cases had better quality of life according to PGWB and SF-36. High-risk genotype HLA-DQ2.5/DQ2.5 was more frequent among familial cases, and four non-HLA SNPs were associated with familial celiac disease.
CONCLUSIONS
Despite the greater proportion of high-risk genotypes, familial cases had milder symptoms at presentation than did sporadic cases. Worse experience of symptoms and poorer quality of life in sporadic disease indicate a need for intensified support.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Celiac Disease; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Young Adult
PubMed: 32705440
DOI: 10.1007/s10620-020-06490-1 -
Internal Medicine (Tokyo, Japan) Jan 2021At 37 years old, a patient developed chronic watery diarrhea, generalized pain, severe hypokalemia and elevated creatine kinase levels. She was thought to have...
At 37 years old, a patient developed chronic watery diarrhea, generalized pain, severe hypokalemia and elevated creatine kinase levels. She was thought to have rhabdomyolysis due to hypokalemia from chronic diarrhea. No organic cause was found. Her symptoms subsided with potassium correction, but hypokalemia persisted; she visited our hospital at 44 years old. Endoscopy detected prominent atrophy of the intestinal villi. Histology indicated Marsh-Oberhuber type-3b disease. Anti-gliadin and anti-tissue transglutaminase IgA antibody tests were positive. She was diagnosed with celiac disease and started on a gluten-free diet, which improved her symptoms. This report is only the tenth of its kind worldwide.
Topics: Adult; Celiac Disease; Duodenum; Female; Gliadin; Humans; Immunoglobulin A; Intestinal Mucosa; Rhabdomyolysis
PubMed: 32921688
DOI: 10.2169/internalmedicine.5358-20 -
The Journal of Clinical Investigation Oct 2023Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by...
Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes. Multiplex immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking antidiarrheal drug crofelemer dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. γ-Secretase inhibition with DAPT recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum/glucocorticoid-regulated kinase 2 (SGK2) and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID.
Topics: Humans; Microvilli; Myosin Heavy Chains; Myosin Type V; Enterocytes; Malabsorption Syndromes; Mucolipidoses
PubMed: 37643022
DOI: 10.1172/JCI169234 -
Recent advances in understanding and managing malabsorption: focus on microvillus inclusion disease.F1000Research 2019Microvillus inclusion disease (MVID) is a rare congenital severe malabsorptive and secretory diarrheal disease characterized by blunted or absent microvilli with... (Review)
Review
Microvillus inclusion disease (MVID) is a rare congenital severe malabsorptive and secretory diarrheal disease characterized by blunted or absent microvilli with accumulation of secretory granules and inclusion bodies in enterocytes. The typical clinical presentation of the disease is severe chronic diarrhea that rapidly leads to dehydration and metabolic acidosis. Despite significant advances in our understanding of the causative factors, to date, no curative therapy for MVID and associated diarrhea exists. Prognosis mainly relies on life-long total parenteral nutrition (TPN) and eventual small bowel and/or liver transplantation. Both TPN and intestinal transplantation are challenging and present with many side effects. A breakthrough in the understanding of MVID emanated from seminal findings revealing mutations in as a cause for MVID. During the last decade, many studies have thus utilized cell lines and animal models with knockdown of to closely recapitulate the human disease and investigate potential therapeutic options in disease management. We will review the most recent advances made in the research pertaining to MVID. We will also highlight the tools and models developed that can be utilized for basic and applied research to increase our understanding of MVID and develop novel and effective targeted therapies.
Topics: Animals; Humans; Malabsorption Syndromes; Microvilli; Mucolipidoses; Myosin Heavy Chains; Myosin Type V
PubMed: 31824659
DOI: 10.12688/f1000research.20762.1 -
Iranian Biomedical Journal Jan 2024Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an... (Review)
Review
Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an inflammatory response is triggered in the small intestine, and this reaction can be alleviated by the elimination of gluten from the diet. The clinical manifestations of CD vary greatly from person to person and begin at a young age or in adulthood. Influence of genetic factors on CD development is evident in carriers of the DQ2 and/or DQ8 allele. HLA genotypes are associated with gut colonization by bacteria, particularly in individuals suffering from CD. In addition, beneficial gut microbes are crucial for the production of DPP-4, which plays a key role in immune function, as well as metabolic and intestinal health. Therefore, probiotics have been recommended as a complementary food supplement in CD.
Topics: Humans; Celiac Disease; Glutens; Alleles; Genetic Predisposition to Disease; Genotype
PubMed: 38444380
DOI: 10.61186/ibj.4028 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2023Celiac disease (CD) is associated with malabsorption and consequential nutritional deficiencies. Patients with CD must follow a gluten-free diet (GFD), which is also...
BACKGROUND
Celiac disease (CD) is associated with malabsorption and consequential nutritional deficiencies. Patients with CD must follow a gluten-free diet (GFD), which is also associated with nutrient deficiencies. Despite the clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD and the usefulness of assessment during follow-up. The aim was to investigate the presence of micronutrient and protein deficiencies in pediatric patients with CD after starting a GFD and receiving standard clinical care, taking disease activity into account.
METHODS
This single center retrospective chart review aimed to map the occurrence of nutrient deficiencies, determined in serum samples derived during follow-up in an expertise center for pediatric CD. Serological micronutrient levels were determined during routine clinical visits up until 10 years in children with CD on a GFD.
RESULTS
The data of 130 children with CD was included. When pooling the measurements between 3 months and 10 years after GFD initiation, a deficiency in iron, ferritin, vitamin D, vitamin B12, folate and zinc was present in 33%, 21,9%, 21,1%, 2,4%, 4,3% and 8,1% of measurements, respectively. No hypocalcemia or vitamin B6 deficiency was found.
CONCLUSION
The prevalence of deficiency varies amongst nutrients in children following a GFD, a high prevalence of some nutrient deficiencies is noteworthy. This study highlights the necessity to structurally investigate the risk of developing nutrient deficiencies while following a GFD. Knowledge of the risk to develop deficiencies can contribute to achieving a more evidence based approach in the management and follow-up of CD in children.
Topics: Humans; Child; Follow-Up Studies; Retrospective Studies; Celiac Disease; Nutrients; Micronutrients
PubMed: 37246082
DOI: 10.1016/j.clnu.2023.05.003