(Epi)catechin damage effects on the development of mouse intestinal epithelial structure through the PERK-eIF2α-ATF4-CHOP pathway.

As powerful bioactive compounds found in a variety of plant-based foods, (epi)catechins have been identified to be associated with an abundant array of health benefits. While their adverse impacts have also been gaining increasing attention, their intestinal impact is still unclear. In this study, intestinal organoids were used as an in vitro model to analyze the effects of four (epi)catechins on the development of the intestinal epithelial structure. Morphological characteristics, oxidative stress, and endoplasmic reticulum (ER) stress assays with (epi)catechins treatment showed that (epi)catechins promoted intestinal epithelial apoptosis and stress response. These effects had dose-dependent and structural differences (EGCG > EGC > ECG > EC). Furthermore, GSK2606414, a protein kinase RNA (PKR)-like ER kinase (PERK) pathway inhibitor, confirmed that the PERK-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) pathway is closely related to the damage. In addition, the results for the intestinal inflammatory mouse model further verified that (epi)catechins significantly delayed intestinal repair. Taken together, these findings revealed that overdosage of (epi)catechins has damage potential on the intestinal epithelium and may increase the risk of intestinal damage.

Respiratory Influenza Virus Infection Causes Dynamic Tuft Cell and Innate Lymphoid Cell Changes in the Small Intestine.

Influenza A viruses (IAV) can cause severe disease and death in humans. IAV infection and the accompanying immune response can result in systemic inflammation, leading to intestinal damage and disruption of the intestinal microbiome. Here, we demonstrate that a specific subset of epithelial cells, tuft cells, increase across the small intestine during active respiratory IAV infection. Upon viral clearance, tuft cell numbers return to baseline levels. Intestinal tuft cell increases were not protective against disease, as animals with either increased tuft cells or a lack of tuft cells did not have any change in disease morbidity after infection. Respiratory IAV infection also caused transient increases in type 1 and 2 innate lymphoid cells (ILC1 and ILC2, respectively) in the small intestine. ILC2 increases were significantly blunted in the absence of tuft cells, whereas ILC1s were unaffected. Unlike the intestines, ILCs in the lungs were not altered in the absence of tuft cells. This work establishes that respiratory IAV infection causes dynamic changes to tuft cells and ILCs in the small intestines and that tuft cells are necessary for the infection-induced increase in small intestine ILC2s. These intestinal changes in tuft cell and ILC populations may represent unexplored mechanisms preventing systemic infection and/or contributing to severe disease in humans with preexisting conditions. IMPORTANCE Influenza A virus (IAV) is a respiratory infection in humans that can lead to a wide range of symptoms and disease severity. Respiratory infection can cause systemic inflammation and damage in the intestines. Few studies have explored how inflammation alters the intestinal environment. We found that active infection caused an increase in the epithelial population called tuft cells as well as type 1 and 2 innate lymphoid cells (ILCs) in the small intestine. In the absence of tuft cells, this increase in type 2 ILCs was seriously blunted, whereas type 1 ILCs still increased. These findings indicate that tuft cells are necessary for infection-induced changes in small intestine type 2 ILCs and implicate tuft cells as regulators of the intestinal environment in response to systemic inflammation.

Nutritional Aspects of Pediatric Gastrointestinal Diseases.

In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively "harmless" nature. Apart from a diet's therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical "side effects", however, it should be emphasized that any dietary modification might have negative consequences on children's growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.

Impact of down-stream processing on functional properties of yeasts and the implications on gut health of Atlantic salmon (Salmo salar).

Yeasts are becoming popular as novel ingredients in fish feeds because of their potential to support better growth and concomitantly ensure good fish health. Here, three species of yeasts (Cyberlindnera jadinii, Blastobotrys adeninivorans and Wickerhamomyces anomalus), grown on wood sugars and hydrolysates of chicken were subjected to two down-stream processes, either direct heat-inactivation or autolysis, and the feed potential of the resulting yeast preparations was assessed through a feeding trial with Atlantic salmon fry. Histological examination of distal intestine based on widening of lamina propria, showed that autolyzed W. anomalus was effective in alleviating mild intestinal enteritis, while only limited effects were observed for other yeasts. Our results showed that the functionality of yeast in counteracting intestinal enteritis in Atlantic salmon was dependent on both the type of yeast and the down-stream processing method, and demonstrated that C. jadinii and W. anomalus have promising effects on gut health of Atlantic salmon.

Differential expression of intestinal genes in necrotic enteritis challenged broiler chickens with 2 different Clostridium perfringens strains.

The primary cause of necrotic enteritis (NE) disease in chickens is the NetB-positive Clostridium perfringens bacterium. Many factors are known to affect the severity of NE in the challenge models of broiler chickens, and one of these factors is the virulence of C. perfringens strain. This study was conducted to evaluate the effect of 2 pathogenic C. perfringens strains in a NE challenge model on gut health and mRNA expression of genes encoding apoptosis, tight junction, immunity, and nutrient transporters in broilers. Day-old Ross-308 male broilers (n = 468) were allocated in a 2 × 3 factorial arrangement of treatments with in-feed antibiotics (no or yes) and challenge (Non, C. perfringens strain NE18, and C. perfringens strain NE36) as the factors. The birds in the challenged groups were inoculated with Eimeria species on day 9 and with a fresh suspension of C. perfringens NE18 or NE36 on day 14 and 15. Sample collection was performed on 2 birds of each pen on day 16. Necrotic enteritis challenge, impaired feed conversion ratio during day 0 to 16 compared with the control group where the effect of the NE36 challenge was more severe than that with NE18 (P < 0.001). The mRNA expression of mucin-2, immunoglobulin-G, occludin (P < 0.001), and tight junction protein-1 (P < 0.05) genes were downregulated in both challenged groups compared with the nonchallenged counterparts. Antibiotic supplementation, on the other hand, increased weight gain, and feed intake in all challenged birds (P < 0.01), but upregulated mucin-5ac and alanine, serine, cysteine, and threonine transporter-1 (P < 0.05) only in the NE18 challenged birds. The challenge with NE36 significantly upregulated caspase-8 and claudin-1 (P < 0.001), but downregulated glucose transporter-2 (P < 0.001) compared with the NE18 challenge. These results suggest that NE challenge is detrimental to the performance of broilers through compromised intestinal health, and different C. perfringens strains can affect the severity of the disease through modulating the expression of intestinal genes encoding proteins responsible for apoptosis, gut integrity, immunity, mucus production, and nutrient transporters.

Disease Course and Treatment Response of Eosinophilic Gastrointestinal Diseases in Children With Liver Transplantation: Long-Term Follow-Up.

INTRODUCTION: To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS: All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS: During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION: EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.

Two nuclear localization signals regulate intracellular localization of the duck enteritis virus UL13 protein.

Duck enteritis virus (DEV) multifunctional tegument protein UL13 is predicted to be a conserved herpesvirus protein kinase; however, little is known about its subcellular localization signal. In this study, through transfection of 2 predicted nuclear signals of DEV UL13 fused to enhanced green fluorescent protein, 2 bipartite nuclear localization signals (NLS) were identified. We found that ivermectin blocked the NLS-mediated nuclear import of DEV UL13, showing that the nuclear localization signal of DEV UL13 is a classical importin α- and ß-dependent process. We constructed a DEV UL13 mutant strain in which the NLS of DEV UL13 was deleted to explore whether deletion of the NLS affects viral replication. Amino acids 4 to 7 and 90 to 96 were predicted to be NLSs, further proving that nuclear import occurs via a classical importin α- and ß-dependent process. We also found that the NLS of pUL13 had no effect on DEV replication in cell culture. Our study enhances the understanding of DEV pUL13. Taken together, these results provide significant information regarding the biological function of pUL13 during DEV infection.

Interactive effect of 2 dietary calcium and phytase levels on broilers challenged with subclinical necrotic enteritis: part 1-broiler performance, gut lesions and pH, bacterial counts, and apparent ileal digestibility.

This study investigated the hypothesis that high dietary calcium (Ca) would stimulate necrotic enteritis (NE) and reduce performance, gut health, and nutrient digestibility, and if increased, phytase would reduce NE. Ross 308 male broilers (n = 768) were randomly distributed to 8 treatments in a factorial arrangement. Factors were NE challenge (no or yes), phytase level (500 or 1,500 FTU/kg using 500 FTU/kg matrix values), and Ca level (0.6 or 1.0% starter, 0.5 or 0.9% grower, 0.4 or 0.8% finisher) with the same level of available P (0.40 S, 0.35 G, and 0.35 F). There were 48 pens, 16 birds per pen and 6 replications. Half of the birds were challenged with Eimeria spp on day 9 and 108 CFU per mL of Clostridium perfringens strain EHE-NE18 on day 14 and 15. Gain was higher in birds fed high phytase on day 14 (P < 0.01), day 21 (P < 0.01), day 28 (P < 0.01), and day 35 (P < 0.01). Birds fed high phytase had greater livability on day 21 (P < 0.01). Ca was more digestible in high-Ca diets on day 16, and an NE × Ca interaction (P < 0.05) showed this effect to be more pronounced in unchallenged than in challenged birds. A challenge × Ca interaction for apparent ileal digestibility (AID) of crude protein (CP) (P < 0.05) indicated lower AID of CP in challenged birds fed high Ca. The challenge decreased AID of Ca (P < 0.01). Ca level had no impact on C. perfringens count, but it decreased Lactobacillus (P < 0.05) and Bifidobacteria (P < 0.05) populations in the ceca. High dietary Ca decreased feed conversion ratio. Overall (42 D), the highest WG was observed in unchallenged birds fed high Ca and high phytase with the lowest WG observed in NE-challenged birds fed low Ca and low phytase. The results suggest that full matrix values for high doses of phytase may be appropriate during NE challenge.

Eosinophilic Gastrointestinal Diseases in Children: A Practical Review.

Primary eosinophilic gastrointestinal diseases (EGIDs) represent a heterogeneous group of disorders characterized by eosinophilic inflammation in the absence of known causes for eosinophilia, selectively affecting different segments of the gastrointestinal tract. While pediatric eosinophilic esophagitis (EoE) is a well-defined disease with established guidelines, Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC) remain a clinical enigma with evidence based on limited anecdotal case reports. Large cross-sectional studies in the US defined a prevalence of EoG and EoGE ranging from 1,5 to 6,4/100.000 and from 2,7 to 8,3/100.000 subjects respectively, while the prevalence of EoC ranges from 1,7 to 3,5/100.000 subjects. Regarding the pathogenesis, it is hypothesized that EGIDs result from the interplay between genetic predisposition, intestinal dysbiosis and environmental triggers. Clinically, EGIDs might present with different and nonspecific gastrointestinal symptoms depending on the involved intestinal tract and the extension of eosinophilic inflammatory infiltrate. The diagnosis of EGIDs requires: 1. recurrent gastrointestinal symptoms, 2. increased eosinophils for high power field in biopsy specimens, 3. absence of secondary causes of gastrointestinal eosinophilia. No validated guidelines are available on the clinical management of patients with EGIDs. Evidence from case reports and small uncontrolled case series suggests the use of dietary and corticosteroids as the first-line treatments. Considering the clinical follow-up of EGIDs, three different patterns of disease course are identified: single flare, recurring course-disease and chronic course-disease. This review will focus on pediatric EGIDs distal to esophagus, including Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC).

Environmental enteric dysfunction: a review of potential mechanisms, consequences and management strategies.

BACKGROUND: Environmental enteric dysfunction (EED) is an acquired enteropathy of the small intestine, characterized by enteric inflammation, villus blunting and decreased crypt-to-villus ratio. EED has been associated with poor outcomes, including chronic malnutrition (stunting), wasting and reduced vaccine efficacy among children living in low-resource settings. As a result, EED may be a valuable interventional target for programs aiming to reduce childhood morbidity in low and middle-income countries. MAIN TEXT: Several highly plausible mechanisms link the proposed pathophysiology underlying EED to adverse outcomes, but causal attribution of these pathways has proved challenging. We provide an overview of recent studies evaluating the causes and consequences of EED. These include studies of the role of subclinical enteric infection as a primary cause of EED, and efforts to understand how EED-associated systemic inflammation and malabsorption may result in long-term morbidity. Finally, we outline recently completed and upcoming clinical trials that test novel interventions to prevent or treat this highly prevalent condition. CONCLUSIONS: Significant strides have been made in linking environmental exposure to enteric pathogens and toxins with EED, and in understanding the multifactorial mechanisms underlying this complex condition. Further insights may come from several ongoing and upcoming interventional studies trialing a variety of novel management strategies.

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.

Lupus enteritis masquerading as Crohn's disease.

BACKGROUND: Systemic lupus erythematosus is an autoimmune disease which can affect multiple organs, resulting in significant mortality and morbidity. Lupus enteritis is one of the rare complications of SLE, defined as vasculitis of the intestinal tract, with supportive biopsy findings and/or image. However, lupus enteritis is seldom confirmed on histology or image and the changes of intestinal mucosa are nonspecific. Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract which affects any part of the gastrointestinal tract. The diagnosis of CD is confirmed by clinical evaluation and a combination of endoscopic, histology, radiology, and/or biochemical investigations. CASE PRESENTATION: Here we report a rare case of a 71-years-old Chinese male has been diagnosed with lupus enteritis which similar to CD in the aspects of endoscopic, histology, and radiology. So far, there are no relevant cases reported. CONCLUSIONS: The endoscopic appearance of lupus enteritis is nonspecific, on the basis of our case, the features of lupus enteritis can be described as spacious, clean and no moss ulcers which discontinuous involved all gastrointestinal tract.

Pretreatment with probiotic Enterococcus faecium NCIMB 11181 ameliorates necrotic enteritis-induced intestinal barrier injury in broiler chickens.

The dysfunction of tight-junction integrity caused by necrotic enteritis (NE) is associated with decreased nutrient absorption and gut injury in broiler chickens. Although probiotic Enterococcus faecium (E. faecium) has been reported to possess immune-regulatory characteristics and can prevent diarrhea in pigs, very little information exists in relation to the specific regulatory impact of E. faecium NCIMB 11181 on NE-induced intestinal barrier injury of broiler chickens. This study was conducted to investigate the protective effects of probiotic E. faecium NCIMB 11181 on NE-induced intestinal barrier injury in broiler chickens. The study also aimed to elucidate the mechanisms that underpin these protective effects. One hundred and eighty Arbor Acres (AA) broiler chicks (one day old) were randomly assigned using a 2 × 2 factorial arrangement into two groups fed different levels of dietary E. faecium NCIMB 11181 (0 or 2 × 108 CFU/kg of diet) and two disease-challenge groups (control or NE challenged). The results showed that NE induced body weight loss, intestinal lesions, and histopathological inflammation, as well as intestinal-cell apoptosis. These symptoms were alleviated following the administration of probiotic E. faecium NCIMB 11181. Pretreatment with probiotic E. faecium NCIMB 11181 significantly upregulated the expression of the Claudin-1 gene encoding a tight-junction protein. Claudin-1 and HSP70 protein expression were also increased in the jejunum regardless of NE infection. Furthermore, NE-infected birds fed with E. faecium displayed notable increases in MyD88, NF-κB, iNOS, PI3K, GLP-2, IL-1ß, IL-4, and HSP70 mRNA expression. E. faecium NCIMB 11181 administration also significantly improved the animals' intestinal microbial composition regardless of NE treatment. These findings indicated that addition of E. faecium NCIMB 11181 to poultry feed is effective in mitigating NE-induced gut injury, possibly by strengthening intestinal mucosal barrier function, as well as modulating gut microflora and intestinal mucosal immune responses.

Modulation of hypoxia-inducible factor-1α/cyclo-oxygenase-2 pathway associated with attenuation of intestinal mucosa inflammatory damage by Acanthopanax senticosus polysaccharides in lipopolysaccharide-challenged piglets.

Intestinal barrier inflammatory damage is commonly accompanied by hypoxia. The hypothesis that dietary Acanthopanax senticosus polysaccharides (ASPS) might modulate the hypoxia-inducible factor-1α (HIF-1α) signalling pathway and contribute to attenuate intestinal injury was tested in lipopolysaccharide (LPS)-challenged piglets. Thirty-six weaned pigs were randomly allocated to one of the following three groups: (1) basal diet + saline challenge; (2) basal diet + LPS challenge; (3) basal diet with 800 mg/kg ASPS + LPS challenge. LPS was injected at 15, 18 and 21 d, and intestinal sections were sampled following blood collection at 21 d . The results showed ASPS reversed (P < 0·05) LPS-induced decrease in average daily feed intake and rise (P < 0·05) of diarrhoea incidence and index. Biochemical index reflecting gut barrier damage and function involving ileal pro-inflammatory cytokines (TNF-α and IL-1ß) and enzyme activity (diamine oxidase and lactase), as well as circulatory d-xylose, was normalised (P < 0·05) in LPS-challenged piglets receiving ASPS. ASPS also ameliorated intestinal morphological deterioration of LPS-challenged piglets, proved by elevated ileal villus height (P < 0·05) and improved appearance of epithelial villus and tight junction ultrastructure. Moreover, ASPS prevented LPS-induced amplification of inflammatory mediators, achieved by depressed ileal mRNA abundance of TNF-α, inducible NO synthase and IL-1ß concentration. Importantly, ileal protein expressions of HIF-1α, cyclo-oxygenase-2 (COX-2) and NFκB p65 were also suppressed with ASPS administration (P < 0·05). Collectively, these results suggest the improvement of mucosal inflammatory damage and diarrhoea in immune stress piglets is possibly associated with a novel finding where HIF-1α/COX-2 pathway down-regulation is involved in NFκB p65-inducible releasing of inflammatory cytokines by dietary ASPS.

ß-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation.

Gastrointestinal toxicity limits the clinical application of abdominal and pelvic radiotherapy and currently has no effective treatment. Intestinal leucine-rich-repeat-containing GPCR 5 (Lgr5)-positive stem cell depletion and loss of proliferative ability due to radiation may be the primary factors causing intestinal injury following radiation. Here, we report the critical role of ß-arrestin1 (ßarr1) in radiation-induced intestinal injury. Intestinal ßarr1 was highly expressed in radiation enteritis and in a radiation model. ßarr1 knockout (KO) or knockdown mice exhibited increased proliferation in intestinal Lgr5+ stem cell, crypt reproduction, and survival following radiation. Unexpectedly, the beneficial effects of ßarr1 deficiency on intestinal stem cells in response to radiation were compromised when the endoplasmic reticulum stress-related protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor-2α (eIF2α) pathway was inhibited, and this result was further supported in vitro. Furthermore, we found that ßarr1 knockdown with small interfering RNA significantly enhanced intestinal Lgr5+ stem cell proliferation after radiation via directly targeting PERK. ßarr1 offers a promising target for mitigating radiation-induced intestinal injury.-Liu, Z., Jiang, J., He, Q., Liu, Z., Yang, Z., Xu, J., Huang, Z., Wu, B. ß-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation.

[Physiopathology and pharmacological perspectives in the treatment of radiation enteritis]. / Physiopathologie et modulation pharmacologique de l'entérite radique.

The small intestine is an organ frequently exposed in abdominal and pelvic irradiations. Acute and late toxicity can sometimes be difficult to manage and can significantly affect the quality of life of patients. Currently there is no guideline on the management of acute and late side effects induced by therapeutic irradiation. The aim of this review is to summarize available data on the pathophysiology of radiation enteritis, and to highlight potential preventive strategies and principles of treatment of radiation enteritis.

Endoscopic Features and Diagnostic Procedures of Eosinophilic Gastroenteritis.

No specific endoscopic features for eosinophilic gastroenteritis (EGE) have been reported previously. This study therefore evaluated the endoscopic findings of six patients with EGE. The diagnosis was confirmed based on gastrointestinal symptoms, pathological findings on biopsy, and the absence of other diseases. The site of the lesion was identified based on eosinophilic infiltration with ≥20 cells per high-power field during a pathological specimen analysis. Flattening of the small intestinal villi was observed in four patients; we speculate that this may be a specific feature in the diagnosis of EGE.

Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorders (EGID) are a group of disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms (J Pediatr Gastroenterol Nutr; Spergel et al., 52: 300-306, 2011). These disorders include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic enteritis (EE), and eosinophilic colitis (EC). Symptoms are dependent not only on the location (organ) as well as extent (layer invasion of the bowel wall). Common symptoms of EoE include dysphagia and food impaction in adults and heartburn, abdominal pain, and vomiting in children. Common symptoms of the other EGIDs include abdominal pain, nausea, vomiting, early satiety, diarrhea, and weight loss. These disorders are considered immune-mediated chronic inflammatory disorders with strong links to food allergen triggers. Treatment strategies focus on either medical or dietary therapy. These options include not only controlling symptoms and bowel inflammation but also on identifying potential food triggers. This chapter will focus on the clinical presentation, pathophysiology, and treatment of these increasingly recognized disorders.