Duodenal Mucosa Research Articles

FOXP3 expression in duodenal mucosa: Unique role in pathogenesis and differential diagnosis of celiac disease

Forkhead box protein P3 (FOXP3) positive regulatory T lymphocytes are indispensable in the inflammatory homeostasis of the gastrointestinal tract and represent a significant subset of regulatory cells in inflammatory, autoimmune, and neoplastic conditions. This study aimed to elucidate the potential of FOXP3 expression in diagnosing and pathogenesis of celiac disease (CD) by comparing duodenal biopsies of CD cases with non-CD ones, some of which had increased intraepithelial lymphocytes (IELs). Two hundred sixty-one duodenal tissues of patients who applied to adult gastroenterology were reevaluated for immunohistochemical analysis. After excluding patients on a gluten-free diet (n = 44), the CD (n = 97) and non-CD (n = 120) groups were divided based on clinical complaints that could be associated with CD (intestinal or extraintestinal), serologic and histologic findings. The specific threshold was determined by receiver operating characteristic (ROC) analysis, and its relationship with CD diagnosis and clinicopathological data was evaluated. ROC analysis offered a “>14” cut-off value for diagnosing CD, for which AUC (Area Under The Curve): 0.968, p < 0.0001, sensitivity: 92.8, specificity: 91.7, positive and negative predictive values were 90 % and 94 %, respectively. High FOXP3 expression was associated with higher IEL, diagnosis of CD, more severe histologic (higher Marsh score) and endoscopic (scalloping) findings, and higher anti-tissue transglutaminase and anti-endomysium IgA titers (p < 0.001). It also correlates with IEL in CD patients and is unaffected by the increase in IEL and the presence of gastric Helicobacter Pylori in the non-CD group. FOXP3 is a sensitive and specific marker for diagnosing CD despite inflammatory conditions resulting from non-CD causes.

Duodenal Adenocarcinoma Arising from Brunner’s Glands, A Rare Case Report

Abstract Introduction/Objective Malignancies arising from the Brunner’s glands in duodenum are exceedingly rare with very few cases reported in the literature. Here, we reported a case of duodenal adenocarcinoma of Brunner’s gland origin that obstructed duodenum and extended to involve the pancreatic head. Methods/Case Report A 48-year-old woman came to the Emergency Department of our hospital with epigastric and right upper quadrant abdominal pain. CT imaging demonstrated a heterogeneously enhancing 8.4 x 5.4 x 6 cm mass involving the duodenal lumen, wall, and pancreatic head. An endoscopic ultrasound showed a large fungating, infiltrative, and ulcerative mass in the second portion of the duodenum distal to the ampulla but not involving it. The pancreatic and common bile ducts were uninvolved. Her endoscopic ultrasound biopsy was positive for adenocarcinoma. CA19-9 levels were normal. The patient received chemotherapy with subsequent Whipple procedure. Gross examination revealed an exophytic, tan-white mass with the epicenter in the duodenal wall obstructing the duodenal lumen and extending to involve the pancreatic head inferiorly. The mass was predominantly solid with a few small mucus cysts. Light microscopy demonstrated moderately differentiated adenocarcinoma with prominent necrosis and inflammation. There are intestinal-type, gastric-type and indeterminate types of epithelia in the carcinoma. There are areas in the duodenal wall where a continuous transition from benign Brunner’s glands to dysplastic glands and then to adenocarcinoma is present. Neither adenoma in the overlying duodenal mucosa nor abnormalities in the pancreatic parenchyma is observed. Immunohistochemical stains showed that the neoplastic cells are positive for CAM 5.2, AE1/AE3, and CK7, while only patchy positivity with CK20 and CDX2. Taken together, a diagnosis of duodenal adenocarcinoma arising from Brunner’s glands was rendered. Results (if a Case Study enter NA) N/A Conclusion More cases are needed in order to establish standard treatment guidelines and determine prognostic factors.

Concurrent occurrence of ulcerative duodenitis and ulcerative colitis displaying unique responses to golimumab and ustekinumab.

Recent studies have reported the occurrence of upper gastrointestinal (UGI) inflammation in patients with ulcerative colitis (UC). However, whether UC-associated UGI and colorectal lesions share pathogenic cytokine profiles and responses to biologics remains unknown. Herein, we report a case of concurrent UC and ulcerative duodenitis (UD) that displayed unique responses to biologic treatment. Although treatment with prednisolone (PSL) failed to induce remission in both disorders, golimumab (GLM) and ustekinumab (UST) were effective against UD and UC, respectively, and remission of both disorders was achieved using UST. Immunofluorescence analyses revealed that numbers of immune cells expressing TNF-α were comparable in both duodenal and rectal mucosa before the treatment. GLM or UST treatment markedly decreased numbers of TNF-α-expressing duodenal immune cells, suggesting the presence of correlation between TNF-α expression and disease activity of UD. In contrast, TNF-α expression was not parallel to disease activity of UC because GLM or PSL failed to induce remission despite a marked reduction in TNF-α expression. Responsiveness to GLM or UST together with immunofluorescence studies suggests that TNF-α and IL-12/23p40 are pathogenic cytokines causing UD and UC, respectively, in the present case.

Review: Food-induced mucosal alterations visualized using endomicroscopy.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time invivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

EP542 - ERCP removal of self-expanding metal stent (SEMS) after 25 months

Abstract This abstract highlights a less-explored complication associated with Endoscopic Retrograde Cholangiopancreatography (ERCP) – the delayed removal of pancreatic or biliary stents. The case study involves a 45-year-old woman with a Self-Expandable Metal Stent (SEMS) in place for an extended period of 2 years. Initially, the patient sought medical attention due to episodic epigastric pain, revealing gallstones partially obstructing the common bile duct. An initial ERCP aimed to extract the stones, but a large stone proved challenging to remove. Subsequently, a temporary Fully Covered Self-Expandable Metal Stent (FC-SEMS) was inserted. A follow-up ERCP was planned to remove both the stone and the stent. However, the patient experienced intolerability during the procedure and developed post-ERCP pancreatitis, leading her to decline the second ERCP. In the following year, the patient faced transient common bile duct (CBD) blockage and ascending cholangitis episodes. After thorough discussion with the medical team, she consented to a second ERCP. During this procedure, it was discovered that the SEMS had ingrowth of duodenal mucosa at the proximal end. Successfully removing the SEMS and stone required using a needle knife to dissect the duodenal mucosa of the stent and flipping the stent inside out, as the tissue around the stent was challenging to access. This case underscores the challenges and risks associated with prolonged stent retention. The abstract strongly recommends against leaving the stent in place for an extended duration and advocates for attempting stent removal through ERCP before considering a surgical approach.

Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis

ObjectivePotential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac...

A clinical case report of aberrant pancreas in the practice of a general practitioner

An aberrant pancreas is a fairly rare developmental anomaly, which, de spite its congenital genesis, is most often found in people of the middle age group. The article presents a clinical case of an aberrant pancreas with localization in the antrum of the stomach in a 52-year-old patient. Congenital pathology has an asymptomatic course for a long time, which is subsequently associated with late diagnosis and the need for a comprehensive examination of the patient. Despite the long-term symptomless course of the pathology, the secretory activity of the ab errant pancreas contributes to persistent inflammation of the gastric and duodenal mucosa, potentiates irreversible pathological changes, and increases the risk of complications, including gastric intestinal metaplasia. The patient under consider ation was diagnosed with a multimorbid chronic pathology of the gastrointestinal tract, which, despite ongoing therapy, was characterized by frequent exacerbations. Due to the established diagnosis, it was possible to prescribe successful conser vative treatment and avoid surgical intervention in this patient. According to the literature, differential diagnosis with malignant neoplasms is necessary. The choice of surgical treatment tactics is determined by the development of complications, among which both obstructive complications (dysphagia, pyloric stenosis, intus susception, intestinal obstruction, obstructive jaundice) and complications specific only to pancreatic tissue, such as pancreatitis, cysts and pseudocysts, ulcerative defects with perforation of the hollow organ, benign and malignant neoplasms, are described. The question of the expediency of surgical treatment of patients in the absence of complications remains debatable to the present day, which causes diffi culties in the management of these patients.

Research Note: Poria cocos polysaccharide alleviates lipopolysaccharide-induced intestinal inflammation and barrier damage in broiler chickens

This study aimed to explore the impact of dietary supplementation of Poria cocos polysaccharide (PCP) on the lipopolysaccharide(LPS)-induced intestinal inflammation, morphology, and barrier damage in broilers. A total of 240 1-day-old male Arbor Acre broilers were randomly divided into 4 groups in a 2 × 2 factorial design comprising PCP supplementation (0 or 2 g/kg PCP from d 1 to 23) and LPS challenge (intraperitoneal injection of 1.5 mg/kg body weight of LPS or the same volume of sterile saline at d 22). Our results showed that compared to the non-LPS-treated groups, the treated birds showed a decrease in the ADG, VH, V/C, and the expression of ZO-1, occludin, claudin 1, and mucin2 in the duodenum and jejunum (P < 0.05). However, dietary PCP supplementation significantly mitigated these effects (P < 0.05) except for mucin2 in the duodenum. Furthermore, LPS treatment increased the levels of sIgA and upregulated the mRNA abundances of IL-1β, IL-6, TNF-α, IFN-γ, TLR-4, and MyD88 both in the duodenal and jejunal mucosa (P < 0.05). Whereas, PCP supplementation significantly reversed the LPS-induced effects on these genes (P < 0.05) except for the TLR-4 and MyD88. However, LPS did not impact the expression of anti-inflammatory IL-10 in the duodenal and jejunal mucosa (P > 0.05). Briefly, this study implied that dietary PCP supplementation could ameliorate intestinal inflammation and mucosal damage of LPS-challenged broilers, improving broiler performance.

Pre-housing fasting and diet physical form impact broiler chicks’ gastrointestinal development along the first week of housing

This study aimed to evaluate body and gastrointestinal development in broilers chicks subjected or not to pre-housing fasting and different diet physical forms during the first week of housing. Nine hundred chicks were distributed into a completely randomized design in a 3×3 factorial arrangement: 0, 24 and 48 hours(h) of fasting; mashed (MM), crushed (CC) and micropelletized (MP) physical forms. For each fasting period, 300 animals were housed in protection circles with 100 chicks each. On days 1, 3, 5 and 7 of feeding, six animals were randomly selected, previously weighed and euthanized to obtain organs biometrical and histological data. Chicks fasted for 24 h and 48 h were lighter compared to the 0 h group and the 24-h fasting x MP interaction had a positive impact on body weight at d7 (P<0.05). Although fasted chicks presented lower body weight, small intestine, liver and gizzard were heavier, and presented greater yolk sac consumption (YSC; P<0.05). There were no alterations in the duodenal mucosa (DM) in pre-housing fasting animals (P>0.05). Despite the diet physical form and pre-housing fasting interactions for villus height (VH) and absorptive area (AA) on d1, only diet physical form affected DM, where greater VH and AA on d7 were observed in CC and MP groups (P<0.05). Animals fed MP after 48 h fasting presented smaller VH and AA compared to chicks fed the same diet after 24 h and were similar to the 0 h group (P<0.05). On d1, YSC was similar among groups of the same diet, but for those fed with MP(P<0.05). The 48 h-fasted group presented heavier intestines relative weights (IRW) at d1(P<0.05). Furthermore, the 0 h group fed with CC presented higher IRW, whereas MP showed the lowest IRW over the first week (P<0.05). The DM development (kinetics) showed an increase in VH and AA overtime in all groups, which was more pronounced in 48 h-fasting chicks throughout the first week, showing the highest increase in VH when fed with MP (P<0.05). VH:CD ratio was similar along the first week in MP groups, regardless of the fasting period but more pronounced in the 24 h group fed MM and CC (P<0.05). Therefore, 24 h fasting associated to MP diet may be the most efficient management practice. Collectively, these findings suggest pre-housing fasting is strongly associated with diet physical form at the first week of housing and should be considered to achieve greater performance in broilers.

Intestinal fructose transporters GLUT5 and GLUT2 in children and adolescents with obesity and metabolic disorders

PurposeThe excessive fructose intake including high-fructose corn syrup (HFCS) may be responsible for increase of obesity occurrence. This study was designed to find potential differences in duodenal fructose transporters on mRNA and protein levels between obese and normal weight children and adolescents. Materials/methodsWe performed a cross-sectional study on a group of 106 hospitalized patients aged 12 to 18. Glucose transporter 2 (GLUT2) and glucose transporter 5 (GLUT5) mRNA as well as protein levels (ELISA and Western blot methods) were assessed in duodenal mucosa biopsies of the patients categorized as obese or normal weight. Additionally, the expression of the aforementioned transporters was analyzed in patients based on the presence of insulin resistance (IR) and metabolic syndrome (MS). ResultsIn children with obesity, increased duodenal protein levels of GLUT5 (Relative protein GLUT5 expression/ACTB) (0.027 ​± ​0.009 vs. 0.011 ​± ​0.006, p ​< ​0.05) but not GLUT2 as compared with the normal weight group, were revealed. No significant differences in duodenal relative GLUT2 and GLUT5 genes expression between the studied groups were found. There was no relationship between the presence of IR or MS and intestinal mRNA GLUT2 and GLUT5 as well as GLUT2 protein expression. ConclusionThe upregulation of the duodenal GLUT5 may contribute to obesity occurrence in children and adolescents.

Intra-ampullary Papillary Tubular Neoplasm (IAPN): Clinicopathologic Analysis of 72 Cases Highlights the Distinctive Characteristics of a Poorly Recognized Entity.

The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model.

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Determination of the Frequency of Celiac Disease in Patients Presenting With Chronic Diarrhea.

Celiac disease (CD) is a chronic inflammatory disorder affecting mainly the digestive system and accounts for more than 50% of adult cases presenting to the gastrointestinal clinic with chronic diarrhea. Therefore, in our study, we aimed to determine the prevalence of CDin patients presenting with chronic diarrhea at the gastroenterology outpatient department of Jinnah Hospital, Lahore. This cross-sectional study was conducted from December 9, 2021, to June 8, 2022, and included 140 patients aged 18 to 50 years with chronic diarrhea. Exclusion criteria were lack of informed consent and history of abdominal trauma or surgery. Data collected included age, gender, family history of CD, and clinical symptoms. Diagnostic measures involved serum tissue transglutaminase antibody IgA and IgGlevels, endoscopy, and duodenal biopsy. Statistical analysis was performed using SPSS version 23 (IBM Corp, Armonk, NY), with a p-value of ≤0.05 considered significant. Among the 140 patients, 80 (57.14%) were males, with a mean age of 21 ± 4.35 years. Common symptoms included weight loss (73.5%), abdominal pain (20.7%), and stunted growth (5.7%). A family history of CD was reported in 14.29% of patients. Endoscopy findings included fissuring of the duodenal mucosa (77.9%), decreased height of duodenal folds (15.7%), and nodularity (6.4%). Histopathological examination revealed Marsh III b (65%), Marsh III c (21.4%), and Marsh III a (9.3%). CD was diagnosed in 23.57% of patients. Significant associations were found between CD and female gender, family history of CD, weight loss, stunted growth, and Marsh III c histopathology. CD was diagnosed in 23.57% of patients with chronic diarrhea. It was more prevalent in females and those with a family history of CD. These findings emphasize the need for considering CD in the differential diagnosis of chronic diarrhea to ensure early detection and management.

Morphometric features of the duodenal wall in piglets during different periods of postnatal and neonatal ontogenesis under the influence of the ‘Globigen Jump Start’ feed additive

The morphological parameters of the small intestinal mucosa, such as villi size and crypts, play a key role in the formation of the intestinal tube’s absorption surface. The number of goblet and enterochromaffin cells indicates the epithelium’s functional condition in terms of mucus secretion and production of catecholamines and hormones (serotonin, dopamine). That is why it is important to study and determine certain morphometric parameters of the duodenal wall in piglets during different periods of neonatal and postnatal development, especially during stress situations, namely weaning and transition to protein feeding. The article presents the resulting effect studies of ‘Globigen Jump Start’ feed additive on the histo-morphological parameters of the piglets’ duodenal mucosa on day 7, 14 and 28 of life. A positive effect on mitigating weaning stress was manifested by a decrease in the quantitative and linear indicators of histoarchitectonics of intestinal wall’s individual morphological components. A significant increase in goblet cells, especially in the experimental group, had a positive impact on the mucopolysaccharide synthesis. The piglets’ gastrointestinal tract physiology involves a complex interaction between the central nervous system, metasympathetic nervous system, APUD system, and endocrine system. Due to these systems, the information is transmitted according to the direct and reverse communication mechanisms in the regulation of the gastrointestinal tract function. An increase in the number of enterochromaffin cells and their nuclei diameter in the experimental group of piglets indicated an increased synthesis of catecholamines and hormones. It has an extremely positive effect on the immune and physiological status of piglets, thus emphasizing the crucial role of serotonin in neuronal metabolism and the formation of stress resistance. The increase in the thickness of the duodenal wall muscle layer, in our opinion, occured due to the active peristalsis, which was enhanced by the action of some catecholamines, which were synthesized in a slightly larger amount under the influence of nutrients making up the ‘Globigen Jump Start’ feed additive.

CELIAC DISEASE: NEW POSSIBILITIES FOR DIAGNOSIS AND MANAGEMENT

Вackground. Celiac disease is an autoimmune disease that occurs in genetically predisposed individuals and is characterized by damage to the mucous membrane of the small intestine due to exposure to gluten. The interest of researchers in gluten-associated diseases is growing every year. The true prevalence of celiac disease is not sufficiently studied due to the rarity of "classic" cases and the higher frequency of atypical and various clinical manifestations of this disease. Manifestation of celiac disease is possible at any age, the disease is more often diagnosed in adults. All this dictates the need to develop new algorithms for examining patients for timely detection and treatment of сеliacia. Aim: To review updated key consensus documents on the diagnosis and treatment of celiac disease. Matherials and methods. The results of scientific research related to celiac disease were searched. The studies that are included were selected based on searches in the online databases PubMed, Web of Science, Scopus, Google Scholar and others and relate to the basic methods of diagnosis and management of celiac disease. 110 sources were selected for analysis, of which were used that met the search criteria. Results. Based on the analysis of experimental and clinical studies, difficulties were identified in diagnosing celiac disease associated with a greater prevalence of extraintestinal manifestations and a rarity of "classical" cases. Methods of approach to the diagnosis of celiac disease in children and adults have been developed, taking into account invasiveness and accessibility. The basic approach in the treatment of celiac disease is a observed gluten-free diet. Regarding the selection of products, the individual characteristics of each patient are taken into account. Conclusion. To verify the diagnosis, adults and children with suspected celiac disease are recommended to perform esophagogastroduodenoscopy with biopsy of the duodenal mucosa at several points. An alternative method of diagnosis can be a combination of a very high level of antibodies of the imonoglobulin (Ig) A class to tissue transglutaminase (TGAs) and positive antibodies to endomysium (anti EMA) in two blood samples, however, no single analysis is 100% specific for celiac disease, and the diagnostic accuracy varies significantly between different laboratories. The only proven effective treatment for celiac disease is a lifelong gluten-free diet. In the absence of a complete clinical and serological response to diet, treatment goals are determined individually for each patient. The development of new treatments for celiac disease continues.

A shared group of bacterial taxa in the duodenal microbiota of undernourished Pakistani children with environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition. The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been a direct collection of small intestinal samples from undernourished children. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3 and 6 months of age and whose wasting (weight-for-length Z-score [WLZ]) failed to improve after a 2-month nutritional intervention underwent esophagogastroduodenoscopy (EGD). Paired duodenal luminal aspirates and duodenal mucosal biopsies were obtained from 43 children. Duodenal microbiota composition was characterized by sequencing bacterial 16S rRNA gene amplicons. Levels of bacterial taxa (amplicon sequence variants [ASVs]) were referenced to anthropometric indices, histopathologic severity in biopsies, expression of selected genes in the duodenal mucosa, and fecal levels of an immunoinflammatory biomarker (lipocalin-2). A "core" group of eight bacterial ASVs was present in the duodenal samples of 69% of participants. Streptococcus anginosus was the most prevalent, followed by Streptococcus sp., Gemella haemolysans, Streptococcus australis, Granulicatella elegans, Granulicatella adiacens, and Abiotrophia defectiva. At the time of EGD, none of the core taxa were significantly correlated with WLZ. Statistically significant correlations were documented between the abundances of Granulicatella elegans and Granulicatella adiacens and the expression of duodenal mucosal genes involved in immune responses (dual oxidase maturation factor 2, serum amyloid A, and granzyme H). These results suggest that a potential role for members of the oral microbiota in pathogenesis, notably Streptococcus, Gemella, and Granulicatella species, warrants further investigation.IMPORTANCEUndernutrition among women and children is a pressing global health problem. Environmental enteric dysfunction (EED) is a disease of the small intestine (SI) associated with impaired gut mucosal barrier function and reduced capacity for nutrient absorption. The cause of EED is ill-defined. One emerging hypothesis is that alterations in the SI microbiota contribute to EED. We performed a culture-independent analysis of the SI microbiota of a cohort of Pakistani children with undernutrition who had failed a standard nutritional intervention, underwent upper gastrointestinal tract endoscopy, and had histologic evidence of EED in their duodenal mucosal biopsies. The results revealed a shared group of bacterial taxa in their duodenums whose absolute abundances were correlated with levels of the expression of genes in the duodenal mucosa that are involved in inflammatory responses. A number of these bacterial taxa are more typically found in the oral microbiota, a finding that has potential physiologic and therapeutic implications.

Effects of guanidino acetic acid and betaine supplementation on growth, dietary nutrient digestion and intestinal creatine metabolism in sheep.

The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen-protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. Eighteen healthy Kazakh rams (27.46±0.10kg of body weight and 3-month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500mg/kg GAA and 1500mg/kg GAA+600mg/kg RPB, respectively. Compared with control group, test group II had increased (p<0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p<0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non-alcoholic fatty liver disease were significantly altered in test group II versus test group I (p<0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B-cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p<0.05). Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity.

Prominent black esophagus, Wischnewsky spots, and black duodenum in a fatal hypothermia case with an underlying diabetic ketoacidosis.

Hypothermia can occur in patients with diabetic ketoacidosis (DKA), and these two conditions can exacerbate each other. Fatal hypothermia and DKA have overlapping features and findings such as Wischnewsky spots (WS), black esophagus, basal subnuclear vacuolization in the renal tubule, dehydration, and increased acetone levels. Therefore, it may be challenging to differentiate or clarify the context of these two conditions. Herein, we report a case of a 49-year-old man with type 1 diabetes who was found lying in his house in mid-winter. He experienced cardiopulmonary arrest 10h after the initial discovery and died at the hospital. On autopsy, florid left cardiac blood was observed. Black discoloration of the distal part of the esophageal mucosa, widespread WS in the gastric mucosa, and black discoloration of the duodenal mucosa were observed. Histologically, neutrophil infiltration in the esophageal mucosa, neutrophil infiltration and bleeding in the gastric mucosa, basal subnuclear vacuolization and Armanni-Ebstein lesion in the renal tubule epithelium in the kidney, and hyalinization of the islets of Langerhans were observed in the pancreas. Blood acetone and β-hydroxybutyrate levels were 538µg/mL and 8947 µmol/L, respectively. Glycated hemoglobin A1c and glucose levels were 16.2% and 883mg/dL, respectively, while C-reactive protein level was 3.64mg/dL. In conclusion, obnubilation due to DKA was assumed to be the underlying cause of hypothermia, and the combination of these two conditions led to the outcome of death. The concurrent presence of these conditions likely contributed to the conspicuous mucosal findings in the upper gastrointestinal tract.

Single cell transcriptomic analysis of the canine duodenum in chronic inflammatory enteropathy and health.

Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve intestinal mucosal inflammatory infiltrates, but histopathological evaluation of intestinal biopsies from dogs with CIE fails to guide treatment, inform prognosis, or correlate with clinical remission. We employed single-cell RNA sequencing to catalog and compare the diversity of cells present in duodenal mucosal endoscopic biopsies from 3 healthy dogs and 4 dogs with CIE. Through characterization of 35,668 cells, we identified 31 transcriptomically distinct cell populations, including T cells, epithelial cells, and myeloid cells. Both healthy and CIE samples contributed to each cell population. T cells were broadly subdivided into GZMAhigh (putatively annotated as tissue resident) and IL7Rhigh (putatively annotated as non-resident) T cell categories, with evidence of a skewed proportion favoring an increase in the relative proportion of IL7Rhigh T cells in CIE dogs. Among the myeloid cells, neutrophils from CIE samples exhibited inflammatory (SOD2 and IL1A) gene expression signatures. Numerous differentially expressed genes were identified in epithelial cells, with gene set enrichment analysis suggesting enterocytes from CIE dogs may be undergoing stress responses and have altered metabolic properties. Overall, this work reveals the previously unappreciated cellular heterogeneity in canine duodenal mucosa and provides new insights into molecular mechanisms which may contribute to intestinal dysfunction in CIE. The cell type gene signatures developed through this study may also be used to better understand the subtleties of canine intestinal physiology in health and disease.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31–71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil–to–n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5–20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD–RF ablation is an option to treat patients with PLE.