The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
Humans ; Intestinal Mucosa/cytology* ; Intestine, Small/cytology* ; Animals ; Inflammatory Bowel Diseases/immunology* ; Celiac Disease/immunology* ; Paneth Cells/immunology*

Untreated celiac disease (CD) leads to an increased risk for hypoglycemia and diabetic complications. However, the diagnosis of CD can be challenging and some extra-gastrointestinal tract manifestations could be a presenting symptom. We report a case of a 29-year-old Indian male with brittle T1DM whose underlying CD was discovered from a work-up for anemia. After an introduction of a gluten-free diet, he gained 5 kgs in two months, was responsive to oral iron supplement, and had stable glycemic control with much less hypoglycemia. Even though this disease is rare in Asian populations, the diagnosis of celiac disease should always be kept in mind when people with T1DM present with unexplained microcytic anemia and/or unexplained hypoglycemia.
Celiac Disease ; Diabetes Mellitus, Type 1

Non-celiac gluten sensitivity (NCGS) is a term that is used to describe individuals who are not affected by celiac disease or wheat allergy, yet they have intestinal and/or extra-intestinal symptoms related to gluten ingestion with improvement of their symptoms upon withdrawing gluten from their diet. Gluten-related disorder groups are manifested by symptoms of gastrointestinal tract disorders, as well as hematological dermatological endocrinological, gynecological, rheumatological and nervous system symptoms. It is believed that NCGS represents heterogeneous groups with different subgroups characterized by different etiologies, clinical histories and clinical courses. There also appears to be an overlap between NCGS and irritable bowel syndrome (IBS). There is a need for establishing strict criteria for diagnosing NCGS. The absence of validated biomarkers remains a significant limitation for research studies on NCGS. New evidence shows that a gluten-free diet may be beneficial for some patients with gastrointestinal symptoms, such as those symptoms commonly found in patients with IBS. Further studies about NCGS are needed.
Abdominal Pain ; Biomarkers ; Celiac Disease ; Diarrhea ; Diet ; Diet, Gluten-Free ; Eating ; Gastrointestinal Diseases ; Gastrointestinal Tract ; Glutens ; Humans ; Irritable Bowel Syndrome ; Nervous System ; Wheat Hypersensitivity

PURPOSE: To evaluate the effect of gluten-free diet (GFD) on hepatitis B surface antibody (HBsAb) concentrations among previously immunized pediatric celiac disease (CD) subjects.METHODS: We retrospectively evaluated pediatric CD subjects in serological remission who were previously immunized for hepatitis B virus as infants. The temporal relationship between HBsAb concentration, the amount of time on a GFD, and age were evaluated.RESULTS: Overall, 373 CD subjects were analyzed: 156 with HBsAb sampled prior to GFD initiation and 217 after initiation of a GFD and in serological remission. Median age at HBsAb concentration measurement for those before and after GFD initiation was 5.3 years (interquartile range [IQR], 3.1–9.2 years) and 7.6 years (IQR, 5.4–10.9 years), respectively (p<0.001). There was no sex difference between the groups. The median time of HBsAb measurement was 2 months (IQR, 0–5.7 months) before and 12.8 months (IQR, 5.3–30.3 months) after initiation of GFD. The HBsAb concentration was low in 79 (50.6%) and 121 (55.7%) subjects before and after GFD initiation, respectively (p=0.350). Age was inversely associated with low HBsAb concentrations. Neither being on a GFD nor sex was associated with low HBsAb concentrations.CONCLUSION: Adherence to a GFD does not affect HBsAb concentration in children with CD. Age is inversely associated with HBsAb concentration.
Antibodies ; Celiac Disease ; Child ; Diet, Gluten-Free ; Glutens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunization ; Infant ; Retrospective Studies ; Sex Characteristics

Artificial intelligence is likely to perform several roles currently performed by humans, and the adoption of artificial intelligence-based medicine in gastroenterology practice is expected in the near future. Medical image-based diagnoses, such as pathology, radiology, and endoscopy, are expected to be the first in the medical field to be affected by artificial intelligence. A convolutional neural network, a kind of deep-learning method with multilayer perceptrons designed to use minimal preprocessing, was recently reported as being highly beneficial in the field of endoscopy, including esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy. A convolutional neural network-based diagnostic program was challenged to recognize anatomical locations in esophagogastroduodenoscopy images, Helicobacter pylori infection, and gastric cancer for esophagogastroduodenoscopy; to detect and classify colorectal polyps; to recognize celiac disease and hookworm; and to perform small intestine motility characterization of capsule endoscopy images. Artificial intelligence is expected to help endoscopists provide a more accurate diagnosis by automatically detecting and classifying lesions; therefore, it is essential that endoscopists focus on this novel technology. In this review, we describe the effects of artificial intelligence on gastroenterology with a special focus on automatic diagnosis, based on endoscopic findings.
Ancylostomatoidea ; Artificial Intelligence ; Capsule Endoscopy ; Celiac Disease ; Colonoscopy ; Diagnosis ; Diagnosis, Computer-Assisted ; Endoscopy ; Endoscopy, Digestive System ; Endoscopy, Gastrointestinal ; Gastroenterology ; Helicobacter pylori ; Humans ; Intestine, Small ; Learning ; Methods ; Neural Networks (Computer) ; Pathology ; Polyps ; Stomach Neoplasms

BACKGROUND/AIMS: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. METHODS: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. RESULTS: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%–85.03%) and interobserver (24.6%–71.5%) agreements. CONCLUSIONS: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD.
Biopsy ; Celiac Disease ; Classification ; Cohort Studies ; Epithelial Cells ; Humans ; Intestine, Small ; Logistic Models ; Lymphocyte Count ; Observer Variation ; Sensitivity and Specificity

Patients with a functional gastrointestinal disorder (FGID) frequently report abdominal discomfort and bloating after ingesting specific foods. However, evidence on the relationship between foods and symptoms is lacking. In addition, the diagnosis of food hypersensitivity and food intolerance does not seem to be established yet. Food hypersensitivity can be divided into immunologically mediated and non-immunologically mediated forms. The immunologically mediated forms are specifically termed food allergies, whereas the non-immunologically mediated forms are referred to as food intolerances. Various diagnostic tools are required to make an accurate diagnosis of a food allergy or a food intolerance. First, a thorough examination of the history and basic tests to rule out other organic diseases are needed. Next, diagnostic tests for immunoglobulin E-mediated food allergies are required and diseases, such as celiac disease and lactose intolerance, should be differentiated. A diagnosis for non-celiac gluten sensitivity (NCGS) is also required. A double blind, randomized, placebo-controlled, dietary challenge test can be used for diagnosing NCGS and food intolerance. Diagnostic tests for food intolerance, in which scientific evidence is lacking, may result in a misdiagnosis of food hypersensitivity or food intolerance in patients with a FGID. Therefore, an accurate diagnosis of food hypersensitivity or food intolerance based on reliable tests is required.
Celiac Disease ; Diagnosis ; Diagnostic Errors ; Diagnostic Tests, Routine ; Food Hypersensitivity ; Gastrointestinal Diseases ; Glutens ; Humans ; Immunoglobulins ; Lactose Intolerance

Excessive weight gain in children diagnosed with celiac disease (CD) is becoming more common. We describe 2 siblings (9-year and 6 months-old female and 6-year and 9 months-old male) with obesity showing attenuated gastrointestinal and atypical symptoms in which CD was diagnosed in the absence of a known family history of CD. After children's diagnosis, CD in their parents was also investigated. It was detected in their father affected by overweight. The presentation of patients with CD has changed. While patients with overweight and obesity commonly have symptoms such as abdominal pain, reflux, headache, and constipation due to lifestyle factors, CD should also be considered in patients with or without a family history of CD. Careful nutritional status assessment and follow-up monitoring after the diagnosis of CD are mandatory, especially in subjects who are already overweight at the presentation of this disease.
Abdominal Pain ; Celiac Disease ; Child ; Constipation ; Diagnosis ; Fathers ; Female ; Follow-Up Studies ; Headache ; Humans ; Life Style ; Nutritional Status ; Obesity ; Overweight ; Parents ; Recognition (Psychology) ; Siblings ; Weight Gain

PURPOSE: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cut-off value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment. METHODS: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cut-off values of anti-tTG. RESULTS: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75–1). CONCLUSION: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75–1). This cut-off may be used in combination with clinical judgment to diagnose CD.
Antibodies ; Biopsy ; Celiac Disease ; Child ; Diagnosis ; Diagnostic Tests, Routine ; Duodenitis ; Gastroenterology ; Humans ; Immunoglobulins ; Judgment ; Observational Study ; ROC Curve ; Sensitivity and Specificity ; Tertiary Care Centers ; Wetlands

BACKGROUND/AIMS: Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. METHODS: Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. RESULTS: After empirical verification, age at diagnosis was considered appropriate in between A1 ( < 18) and A2 (≥18). The disease presentation has been classified into 3 types–P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. CONCLUSIONS: APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis.
Age of Onset ; Celiac Disease* ; Classification* ; Consensus ; Diagnosis ; Expert Testimony ; Global Health ; Humans ; India