Enteropathy Research Articles

Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

BackgroundEnvironmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. MethodsNon-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2years of age. FindingsChildren in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. InterpretationThe large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. FundingBill & Melinda Gates Foundation.

Can Celiac Disease Present Along With Childhood Obesity

Celiac disease is an autoimmune, gluten-induced enteropathy with a prevalence of 1-1.5% in Western populations. It may present with classical gastrointestinal symptoms, non-gastrointestinal symptoms or as an asymptomatic disease. Cases of childhood obesity in gluten sensitive enteropathy have been recently reported. The study aimed to retrospectively evaluate the rate of overweight and obesity prevalence in a large sample of celiac children in comparison to non-celiac group, and to investigate the weight dynamics following gluten-free diet. Among 390 patients, 68 (17.4%) (29 boys) were overweight or obese at diagnosis. Gluten-free diet did not shown a beneficial effect on weight. The study demonstrates comparable rates of overweight and obesity in celiac versus non-celiac population.

Mucosal Recovery and Mucosal Healing in Biopsy-Defined Adult Celiac Disease

Celiac disease (gluten-sensitive enteropathy) is an immune mediated disorder with characteristic histopathological small bowel mucosal changes that respond to a strict gluten-free diet. Recent studies have suggested that complete (rather than partial) mucosal recovery and healing is possible, but in some this may require a more prolonged period than is currently appreciated. In this study, 182 patients (60 males, 122 females) referred for evaluation of symptoms, including diarrhea and weight loss, were selected only if initial biopsies showed characteristic inflammatory changes with severe architectural disturbance. All patients were treated with a strict gluten diet alone and diet compliance regularly monitored. Up to 90% or more of patients showed a complete mucosal response or healing. A time-dependent rate of response was noted with most patients requiring more than 1 year, and even 2 years or more, to respond, however, complete mucosal healing was still possible within 6 months. In this evaluation, females in each of 4 different age ranges had mucosal response and healing rates superior to males, while elderly celiacs had lower rates. Such factors should be considered before labeling a patient with “non-responsive” disease. However, inflammatory changes with persistent architectural disturbance, especially in celiacs with a late diagnosis and resultant late initiation of a gluten-free diet treatment, may be at increased risk for a later small bowel complication, including lymphoma.

Rifaximin and NSAID Enteropathy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with small-intestinal damage ranging from increased permeability to frank ulceration. The

Protein-losing Enteropathy in Association with Right Heart Failure

A 65-year-old woman, with past history of mitral valve replacement, developed severe right heart failure. In addition to elevated right heart pressure, she had significant hypoalbuminemia as the important cause of refractory edema. Technetium-99m-labelled human serum albumin scintigraphy showed leak of protein from the transverse colon and the excretion of alpha 1 antitrypsin in the stool was markedly increased. Diagnosis of protein losing enteropathy was established. The etiology was increased lymphatic pressure secondary to right heart failure of multifactorial cause, including elevated left side filling pressures and out of proportion pulmonary hypertension due to old tuberculosis, resulting in significant tricuspid regurgitation. The patient was managed conservatively with increased dose of furosemide from 10-20mg every other day up to 40-60mg/day, and maximum dose of tolvaptan (a vasopressin 2 receptor blocker) of 15mg/ day, in addition to high protein diet.

Bilateral Serous Macular Elevation Associated with Lupus Protein-losing Enteropathy.

Bilateral Serous Macular Elevation Associated with Lupus Protein-losing Enteropathy.

Duhring Brocq Disease: The First Manifestation of Celiac Disease in an Adolescent

Dermatitis herpetiformis (Duhring Brocq disease) is an autoimmune inflammatory disease determining polymoprhic pruriginous lesions. It is always associated with a gluten sensitive enteropathy which is most frequently clinically silent. The diagnosis is made on the basis of clinical, serological (IgA antitransglutaminase antibodies and antiendomysial antibodies), hystological and immunollogical (granular immunglobulin A deposits in the papilarry dermis by direct immunofluorescence) data. We present the case of an adolescent with dermatitis herpetiformis associated with atypical celiac disease. The particularity of the case was the abscence of other celiac disease manifestations and the finding of a cutaneous abscess infected with Staphiloccocus aureus, facilitated by the excoriated lesions caused by scratching, which was afterwards complicated with septic arthritis. After 6 weeks of gluten-free diet the cutaneous lesions dissapeared and the pruritus diminished.

早期発症型炎症性腸疾患と免疫不全【JST・京大機械翻訳】

The etiology of inflammatory bowel disease(IBD) is complex and multifactorial.Recent genetic association studies within large IBD cohorts have identified 163 genetic loci.But these 163 loci in total explain 13.6% of Crohn′s disease and 7.5% of ulcerative colitis total disease variance.The classification defines very early-onset IBD as diagnosis before the age of 5 years old, and also before the age of 6 years old in some research.It is likely that genetic factors contribute more to the etiology of very early-onset IBD.Recently some cases have been reported, which have linked to very early-onset IBD, such as IL-10 and IL-10 receptor gene mutation, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, X-linked lymphoproliferative syndrome, IL-21 deficiency, mevalonate kinase deficiency, and so on.And many of these diseases are classified as primary immunodeficiencies.This paper introduces these series of very early-onset IBD in brief. Key words: Very early-onset; Inflammatory bowel disease; Immunodeficiency

Chronic nonspecific multiple ulcers of the small intestine (CNSU) and chronic enteropathy associated with SLCO2A1 (CEAS).

Chronic nonspecific multiple ulcers of the small intestine (CNSU) and chronic enteropathy associated with SLCO2A1 (CEAS).

Progresses in diagnosis and treatment of food protein-induced enteropathy

Food protein-induced enteropathy(FPE)is a series symptom of chronic diarrhea, malabsorption, hypoproteinemia, malnutrition caused by non-IgE mediated food allergy.The pathogenesis of FPE remains unclear, and may be related to gut mucosal barrier, intestinal bacteria, gastrointestinal immunity, oral tolerance and genetic, etc.Histology performance of FPE is characterized by flat atrophy of the small intestine.Diagnosis of PFE relies on history, mucosal histological changes, and oral food challenges.Food eliminate is the mainstay of FPE management.The paper reviews the pathogenesis, clinical manifestation, diagnosis and treatment of FPE to improve the recognition of clinicians. Key words: Food protein-induced enteropathy; Food allergy; Non-IgE mediated; Diagnosis; Treatment

MRI appearances of Gluten⁃induced enteropathy

MRI appearances of Gluten⁃induced enteropathy

A case of Ménétrier's disease seemingly caused by hilar cholangiocarcinoma.

A 54-year-old man presented to our department with abdominal discomfort and anorexia and was diagnosed as having Ménétrier's disease (MD) with hilar cholangiocarcinoma. Based on his clinical examination, there was no evidence of Helicobacter pylori or cytomegalovirus (CMV) infection. Although we administered proton pump inhibitor and high-calorie enteral nutrition, hypoproteinemia did not improve, and the refractory protein-losing enteropathy persisted. However, interestingly, MD improved immediately after resection of the hilar cholangiocarcinoma. Generally, the etiology of MD is unknown, but H. pylori and CMV infections have been implicated. To our knowledge, there has been no previous report indicating that a malignant tumor could be involved in the etiology of MD. Thus, we report an extremely rare case of MD which is seemingly caused by malignancy.

Effect of Proton-Pump Inhibitors on NSAID-Induced Enteropathy

It is well established that proton-pump inhibitors (PPIs) reduce the risk for upper gastrointestinal bleeding from nonsteroidal anti-inflammatory drugs (NSAIDs), but some data suggest they may exacerbate NSAID-associated enteropathy. Investigators in Japan performed an industry-funded, randomized, placebo-controlled study in 60 healthy volunteers. After a baseline capsule endoscopy (CE), participants were randomized to receive celecoxib (200 mg twice daily) with either rabeprazole (20 mg) or …

The role of EpCAM in physiology and pathology of the epithelium.

Epithelial Cell Adhesion Molecule (EpCAM) has been discovered as one of the first tumor-specific antigens overexpressed in epithelial cancer. The present review focuses on the role of EpCAM in physiology and homeostasis of epithelia. Recent research pointed to a close interaction of EpCAM with other cell-cell contact molecules like E-cadherin and claudins and an intimate crosstalk with Wnt and TGF-beta signaling in the regulation of cell growth. Moreover, EpCAM has been shown to modulate trans-epithelial migration processes of white blood cells. Mutations of the EpCAM gene lead to disturbances of epithelial homeostasis and cellular differentiation from the stem cell compartment. In the intestinal tract EpCAM mutations contribute to congenital tufting enteropathy. Regarding tumorigenesis EpCAM can act as an oncogene still depending on additional driver mutations and epithelial phenotype of tumor cells. Tumor cells display increased EpCAM expression that often correlates with the loss of strict basolateral localization. Many tumors show enhanced regulated intramembrane proteolysis (RIP) of EpCAM and loose EpCAM expression under conditions of epithelial to mesenchymal transition. The resulting extracellular EpEX and intracellular EpICD fragments mediate proliferative signals to the cell. Resulting fragments can be validated either by sensitive enzyme-linked immune-sandwich assays (EpEX) or by immunohistochemistry (EpICD). The present review gives an overview on the detection of EpCAM fragments as predictive markers for disease progression and survival of cancer patients.

A case report of adult autoimmune enteropathy and literature review

One case was selected from our hospital and another 31 cases from literature. Symptoms, endoscopic and pathological manifestations and autoimmune examinations of all cases were summarized and analyzed. Their major symptoms were prolonged diarrhea (100%) and malabsorption (100%). Specific small bowel histology indicated villous blunting and minimal intraepithelial lymphocytosis. And 15 of them had some other autoimmune diseases. And many positive autoimmune antibodies were detected, including anti-enterocyte antibodies (n=20), anti-intestinal goblet cell antibody (n=7) and anti-nuclear antibody (n=9). Most patients (27/32) responded to corticosteroids. Adult autoimmune enteropathy is a rare syndrome with intractable diarrhea and malabsorption. And it may be accompanied by other autoimmune diseases in some cases. Key words: Diagnosis; Treatment; Adult autoimmune enteropathy

A Case of NSAIDs-Induced Enteropathy Presenting 25 Years After Stopping NSAIDs

A Case of NSAIDs-Induced Enteropathy Presenting 25 Years After Stopping NSAIDs

Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh

BackgroundEnvironmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. MethodsWe conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. FindingsEE was present in greater than 80% of infants by 12weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ<−2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. InterpretationEE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention. FundingThe Bill and Melinda Gates Foundation (OPP1017093).

Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.

Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease.

Food allergy and the related diseases of digestive system

Food allergy refers to the body's abnormal immune response to food, which induces disorder and/or injuries of human body, and thus triggers a series of manifestations.Ninety percent of food allergy is due to the following allergen: milk, eggs, peanuts, nuts, seafood, soy, wheat, etc.The symptoms of digestive system are closely associated with the nature of allergen (including protein's family nature, three dimensional structure, biological activity and stability) and the body's own status (genetic factors, integrity of intestinal mucosal barrier and oral immune tolerance). The symptoms of digestive systems are not typical, and differ by various factors like body conditions, ages, regions and allergens, so the diagnosis is difficult.Food allergy is categorized by its mechanism: IgE, non IgE, and mix.The symptoms of digestive systems include vomiting, diarrhea, reflux, constipation and abdominal pain, etc, and relative diseases include food protein-induced enteropathy, food protein-induced enterocolitis syndrome, food protein-induced enterocolitis syndrome, food protein-induced proctocolitis, celiac disease, eosinophilic gastroenteritis, eosinophilic esophagitis and infantile colic, etc.Delayed diagnosis will result in failure to thrive, anemia and hypoproteinemia.Therefore, early diagnosis and treatment can effectively prevent malnutrition and improve the children's animation. Key words: Food allergy; Digestive systems; Child

Comparison of CT enterography(CTE) and capsule endoscopy(CE) for small bowel diseases

Objective To compare the role of CTE and CE on the diagnosis of small bowel diseases and evaluate their advantages in patients with different indications. Methods Patients underwent both CTE and CE(interval time<2 weeks) at our institution in recent 3 years were enrolled. The positive detection rates, lesion properties and characteristics of CTE and CE were compared. The diagnostic accuracy of combined method was also analyzed. Results A total of 47 patients were enrolled and the indications included suspected or established Crohn′s disease(28 cases), unexplained abdominal pain(14 cases), obscure gastrointestinal bleeding(3 cases), insufficient small bowel obstruction(1 case) and protein losing enteropathy(1 case). Diagnostic yield of CTE and CE for whole small bowel disorders showed no significant difference(CE 83.0% VS CTE 78.7%, P=0.791). For suspected or established CD, CE had a higher diagnostic accuracy than CTE(78.6% VS 35.7%, P=0.002), especially in detecting lesions in the jejunum(CE 50.0% VS CTE 7.1%, P=0.002). The diagnostic accuracy reached 100.0% when two methods were combined. For unexplained abdominal pain, no significant difference was found in the diagnostic accuracy of CE and CTE(CTE 42.8% VS CE 50.0%, P=1.000). Diagnostic accuracy of combining CTE and CE was 85.7%. Conclusion CTE and CE are both valuable in detecting small bowel lesions. For patients with suspected or established CD, CE is better than CTE. For patients with unexplained abdominal pain, a combination of CTE and CE may be a better strategy than use CTE or CE alone. Key words: Capsule endoscopes; Small bowel; CT enterology