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JCI Insight Feb 2022The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role...
The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8+ T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69+CD103hi) cells were the predominant CD8+ T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103+CD8+ T cells were localized in the intraepithelial region, while CD103-CD8+ T cells and CD4+ T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8+ T cells were enriched in the CD69+CD103-/lo population. However, the duodenal HIV-specific CD8+ Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8+ Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4+ T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies.
Topics: Adult; CD8-Positive T-Lymphocytes; Duodenum; Female; HIV; HIV Infections; Humans; Immunologic Memory; Lymphocyte Activation; Lymphocyte Count; Male
PubMed: 35132966
DOI: 10.1172/jci.insight.154195 -
Cell and Tissue Research Aug 2016Guanylin (GUCA2A/Guca2a/GN) and uroguanylin (GUCA2B/Guca2b/UGN) are expressed in the gastrointestinal tract and have been implicated in ion and fluid homeostasis,...
Guanylin (GUCA2A/Guca2a/GN) and uroguanylin (GUCA2B/Guca2b/UGN) are expressed in the gastrointestinal tract and have been implicated in ion and fluid homeostasis, satiety, abdominal pain, growth and intestinal barrier integrity. Their cellular sources are debated and include goblet cells, entero-/colonocytes, enteroendocrine (EE) cells and tuft cells. We therefore investigated the cellular sources of GN and UGN mRNAs in human and rat duodenal and colonic epithelium with in situ hybridization (ISH) to determine co-expression with Chromogranin A (CHGA/Chga/CgA; enterochromaffin [EC] cells), defensin alpha 6 (DEFA6/Defa6; Paneth cells), mucin 2 (MUC2/Muc2; goblet cells) and selected tuft cell markers. GUCA2A/Guca2a expression was localized to goblet cells and colonocytes in human and rat colon. In human duodenum, GUCA2A was expressed in Paneth cells and was scarce in villous epithelial cells. In rat duodenum, Guca2a was only localized to goblet cells. Guca2b was focally expressed in rat colon. In human and rat duodenum and in human colon, GUCA2B/Guca2b was expressed in dispersed solitary epithelial cells, some with a tuft cell-like appearance. Neither GUCA2A nor GUCA2B were co-expressed with CHGA in human duodenal cells. Consequently, EC cells are probably not the major source of human GN or UGN but other EE cells as a source of GN or UGN are not entirely excluded. No convincing overlap with tuft cell markers was found. For the first time, we demonstrate the cellular expression of GUCA2B in human duodenum. The specific cellular distribution of both GN and UGN differs between duodenum and colon and between human and rat intestines.
Topics: Animals; Cell Count; Colon; Duodenum; Female; Gastrointestinal Hormones; Humans; In Situ Hybridization; Intestinal Mucosa; Natriuretic Peptides; Rats; Rats, Sprague-Dawley
PubMed: 27044258
DOI: 10.1007/s00441-016-2393-y -
PloS One 2022This study examined the correlation between pancreatic microbiome and patients characteristics. Furthermore, we compared different duodenal materials to examine their...
BACKGROUND/OBJECTIVES
This study examined the correlation between pancreatic microbiome and patients characteristics. Furthermore, we compared different duodenal materials to examine their reflection of the pancreatic microbiome.
METHODS
Patients undergoing pancreatic surgery were included in the study. Characteristics of those patients were prospectively registered and sterile pancreatic biopsies were collected during surgery. After completion of the resection, duodenal fluid, -tissue and -swab were collected. Bacterial DNA was extracted and analyzed with IS-pro assay.
RESULTS
Paired samples of 51 patients were available for evaluation, including pancreatic biopsies from all patients, 22 duodenal fluids, 21 duodenal swabs and 11 duodenal tissues. The pancreatic microbiome consisted mostly of Proteobacteria followed by Firmicutes, Actinobacteria, Fusobacteria and Verrucomicrobia (FAFV) and Bacteroidetes. On species level, Enterococcus faecalis, Escherichia coli, and Enterobacter-Klebsiella were most abundant. In pancreatic biopsies, the total bacterial load and Proteobacteria load were significantly higher in patients with biliary drainage (54618.0 vs 5623.5; 9119.0 vs 2067.1). Patients who used proton pump inhibitors had a significantly higher total bacterial load (115964.7 vs 8495.8), more FAFV (66862.9 vs 1890.1), more Proteobacteria (24245.9 vs 2951.4) and more Bacteroidetes (542.5 vs 25.8). The head of the pancreas contained significantly more bacteria (21193.4 vs 2096.8) and more FAFV (5225.7 vs 19.0) compared to the tail, regardless of biliary drainage. Furthermore, the microbiome of all duodenal materials showed a weak correlation with the pancreatic microbiome.
CONCLUSION
Biliary drainage, use of proton pump inhibitors, and anatomic location of the pancreatic biopsy influence the pancreatic microbiome. Furthermore, the duodenal microbiome does not suffice as a surrogate for the pancreatic microbiome.
Topics: Humans; Proton Pump Inhibitors; Microbiota; Duodenum; Pancreas; Bacteria; Bacteroidetes; Proteobacteria; Fusobacteria; RNA, Ribosomal, 16S
PubMed: 36525425
DOI: 10.1371/journal.pone.0278377 -
Cellular and Molecular Gastroenterology... 2021Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process... (Observational Study)
Observational Study
BACKGROUND & AIMS
Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed.
METHODS
Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist.
RESULTS
An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation.
CONCLUSIONS
Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD.
Topics: Adult; Amides; Animals; Biopsy; Case-Control Studies; Disease Models, Animal; Duodenum; Dyspepsia; Ethanolamines; Female; Gastric Acid; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Male; Mast Cells; Mice; Mice, Knockout; Middle Aged; PPAR alpha; Palmitic Acids; TRPV Cation Channels; Tissue Culture Techniques
PubMed: 33065341
DOI: 10.1016/j.jcmgh.2020.10.001 -
World Journal of Gastroenterology Feb 2016To investigate the advantages of inferoposterior duodenal approach (IPDA) for laparoscopic pancreaticoduodenectomy (LPD).
AIM
To investigate the advantages of inferoposterior duodenal approach (IPDA) for laparoscopic pancreaticoduodenectomy (LPD).
METHODS
A total of 36 patients subjected to LPD were admitted to the Affiliated Yijishan Hospital of Wannan Medical College from December 2009 to February 2015. These patients were diagnosed with an ampullary tumour or a pancreatic head tumour through computed tomography, magnetic resonance imaging or endoscopic retrograde cholangiopancreatography preoperatively. The cases were selected on the basis of the following criteria: tumour diameter < 4 cm; no signs of peripheral vascular invasion; evident lymph node swelling; and distant metastasis. Of the 36 cases, 20 were subjected to anterior approach (AA; AA group) and 16 were subjected to IPDA (IPDA group). Specimen removal time, intraoperative blood loss and postoperative complications in the two groups were observed, and their differences were compared.
RESULTS
During the operation, 2 cases in the AA group and 2 cases in the IPDA group were converted to laparotomy; these cases were excluded from statistical analysis. The remaining 32 cases successfully completed the surgery. The AA group and IPDA group exhibited the specimen removal time of 205 ± 52 and 160 ± 35 min, respectively, and the difference was significant (P < 0.01). The AA group and IPDA group revealed the intraoperative blood loss of 360 ± 210 mL and 310 ± 180 mL, respectively, but these values were not significantly different. Postoperative pathological results revealed 4 cases of inferior common bile duct cancer, 8 cases of duodenal papillary cancer, 6 cases of ampullary cancer, 13 cases of pancreatic cancer, 3 cases of chronic pancreatitis accompanied with cyst formation or duct expansion, and 2 cases of mucinous cystic tumour in the pancreatic head. The postoperative complications were pulmonary Staphylococcus aureus infection, incision faulty union, ascites induced poor drainage accompanied with infection, bile leakage, pancreatic leakage and delayed abdominal bleeding.
CONCLUSION
In IPDA, probing for important steps can be performed in early stages, surgical procedures can be optimised and operation time can be shortened.
Topics: Adult; Aged; Ampulla of Vater; Blood Loss, Surgical; China; Common Bile Duct Neoplasms; Duodenum; Female; Humans; Laparoscopy; Male; Middle Aged; Operative Time; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26877619
DOI: 10.3748/wjg.v22.i6.2142 -
Surgery For Obesity and Related... Jun 2022Discovering the role duodenal exclusion plays in weight loss and resolution of type 2 diabetes (T2D) may help refine the surgical and nonsurgical treatment of obesity...
BACKGROUND
Discovering the role duodenal exclusion plays in weight loss and resolution of type 2 diabetes (T2D) may help refine the surgical and nonsurgical treatment of obesity and T2D.
OBJECTIVES
To assess changes in glucose homeostasis due to duodenal exclusion using a duodenal-jejunal bypass liner (DJBL) in a nonobese canine model.
SETTING
Academic laboratory setting.
METHODS
An intravenous glucose tolerance test (IVGTT), and a mixed-meal tolerance test (MMTT) at baseline, 1, and 6 weeks post DJBL implantation (I1 and I6, respectively), and 1 and 6 weeks post DJBL removal (R1 and R6, respectively) were done in canines (n = 7) fed a normal chow diet.
RESULTS
Placement of the DJBL induced weight loss that was maintained until 4 weeks post removal (R4), despite normal food intake. Total bile acids (TBA) and glucagon-like peptide-1 (GLP-1) during the MMTT were significantly increased at I1 and were associated with increased lactate and free fatty acids. Hypoglycemia counter-regulation was blunted during the IVGTT at I1 and I6, returning to baseline at R1. While there were no changes to insulin sensitivity during the experiment, glucose tolerance was significantly increased following the removal of the DJBL at R1.
CONCLUSION
These data show that in a normoglycemic, nonobese canine model, duodenal exclusion induces energy intake-independent weight loss and negative metabolic effects that are reversed following re-exposure of the small intestine to nutrients.
Topics: Animals; Bariatric Surgery; Blood Glucose; Diabetes Mellitus, Type 2; Dogs; Duodenum; Glucose; Homeostasis; Humans; Jejunum; Treatment Outcome; Weight Loss
PubMed: 35361540
DOI: 10.1016/j.soard.2022.02.012 -
Journal of Tropical Pediatrics Jan 2021There is insufficient knowledge on the * duodenal histology and Helicobacter pylori infection in malnourished Bangladeshi children. Therefore, we attempted to explore...
AIM
There is insufficient knowledge on the * duodenal histology and Helicobacter pylori infection in malnourished Bangladeshi children. Therefore, we attempted to explore the prevalence of H. pylori infection and duodenal histopathology in 2-year-old chronic malnourished Bangladeshi slum-dwelling children and investigate their association with dyspeptic symptoms.
METHODS
This cross-sectional study was conducted using the data of the Bangladesh Environmental Enteric Dysfunction study in an urban slum of Dhaka, Bangladesh. With a view to address the association of environmental enteric dysfunction (EED) with stunting, upper gastrointestinal endoscopy was performed on 54 chronic malnourished children {31 stunted [length-for-age Z-scores (LAZ) <-2] and 23 at risk of stunting (LAZ <-1 to -2)} aged between 12-24 months and the mucosal biopsies were subjected to histopathological examination after obtaining proper clinical history. Stool antigen for H. pylori (HpSA) was assessed to determine H. pylori status.
RESULTS
In all, 83.3% (45/54) of the children had histopathological evidence of duodenitis. Chronic mild duodenitis was found to be the most prevalent form of duodenitis (53.7%) in the children. Only 8.9% (4/45) of the children with duodenitis had dyspepsia (p < 0.05). The 14.8% (8/54) of the children were found positive for H. pylori infection. Logistic regression analysis revealed children positive for HpSA had significant association with dyspepsia (OR 9.34; 95% CI 1.54-56.80).
CONCLUSIONS
The number of chronic malnourished children suffering from duodenitis was found to be very high. Majority of these children was asymptomatic. Children positive for HpSA had significant association with dyspeptic symptoms.
Topics: Bangladesh; Child; Child, Preschool; Cross-Sectional Studies; Duodenitis; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Infant; Poverty Areas
PubMed: 33099650
DOI: 10.1093/tropej/fmaa079 -
Medicina (Kaunas, Lithuania) Jun 2022: Traumatic duodenal injury is a rare disease with limited evidence. We aimed to evaluate the risk factors for postoperative leakage and outcomes of pyloric exclusion... (Review)
Review
: Traumatic duodenal injury is a rare disease with limited evidence. We aimed to evaluate the risk factors for postoperative leakage and outcomes of pyloric exclusion after duodenal grade 2 and 3 injury. : We reviewed a prospectively collected trauma database for the period January 2004-December 2020. Patients with grade 2 and 3 traumatic duodenal injury were included. To identify the risk factors for postoperative leakage, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) logistic model. We constructed a receiver operator characteristic (ROC) curve to predict risk factors for postoperative leakage. : During the 17-year period, 179,887 trauma patients were admitted to a regional trauma center in Korea. Of these patients, 74 (0.04%) had duodenal injuries. A total of 49 consecutive patients had grade 2 and 3 traumatic duodenal injuries and underwent laparotomy. The incidence of postoperative leakage was 32.6% (16/49). Overall mortality was 18.4% (9/49). A stepwise multivariable logistic regression and LASSO logistic regression model showed that time from injury to initial operation was the sole statistically significant risk factor. The ROC curve at the optimal threshold of 15.77 h showed the following: area under ROC curve, 0.782; sensitivity, 68.8%; specificity, 87.9%; positive predictive value, 73.3%; and negative predictive value, 85.3%. There was no significant difference in outcomes between primary repair alone and pyloric exclusion. : Time from injury to initial operation may be the sole significant risk factor for postoperative duodenal leakage. Pyloric exclusion may not be able to prevent postoperative leakage.
Topics: Duodenum; Humans; Postoperative Period; Retrospective Studies; Risk Factors; Trauma Centers
PubMed: 35744064
DOI: 10.3390/medicina58060801 -
Experimental Physiology Jul 2017What is the central question of this study? Small intestinal epithelium is exposed to high concentrations of short-chain fatty acids (SCFAs), but their role in...
What is the central question of this study? Small intestinal epithelium is exposed to high concentrations of short-chain fatty acids (SCFAs), but their role in regulating intestinal mucosal barrier function and motility is not fully understood. What is the main finding and its importance? By perfusing the duodenal segment in anaesthetized rats, we show that acetate and propionate significantly decrease mucosal paracellular permeability and transepithelial net fluid flux and increase mucosal bicarbonate secretion. Likewise, SCFAs administered i.v. decrease mucosal permeability but decrease bicarbonate secretion. Altered luminal chemosensing or aberrant signalling in response to SCFAs might contribute to symptoms observed in patients with suppressed mucosal barrier function. Short-chain fatty acids (SCFAs) are produced by bacterial fermentation in the large intestine, particularly from diets containing fibres and carbohydrates. The small intestinal epithelium is exposed to SCFAs derived mainly from oral bacteria or food supplementation. Although luminal nutrients are important in regulation of intestinal functions, the role of SCFAs in regulation of small intestinal mucosal barrier function and motility has not been fully described. The aim of the present study was to elucidate the effects of acetate and propionate on duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30 mm segment of proximal duodenum with an intact blood supply was perfused. The effects on duodenal bicarbonate secretion, blood-to-lumen clearance of Cr-EDTA, motility and transepithelial net fluid flux were investigated. Perfusion of the duodenum with acetate or propionate significantly decreased mucosal paracellular permeability and transepithelial net fluid flux and significantly increased bicarbonate secretion. Acetate or propionate administered as an i.v. infusion decreased the mucosal paracellular permeability, but significantly decreased bicarbonate secretion. Luminal SCFAs changed the duodenal motility pattern from migrating motor complexes to fed patterns. Systemic administration of glucagon-like peptide-2 induced increases in both bicarbonate secretion and net fluid absorption, but did not change motility. Glucagon-like peptide-2 infusion during luminal perfusion of SCFAs significantly reduced the motility. In conclusion, SCFAs decreased duodenal paracellular permeability and net fluid flux. Short-chain fatty acids induced opposite effects on bicarbonate secretion after luminal and i.v. administration. Presence of SCFAs in the lumen induces fed motility patterns. Altered luminal chemosensing and aberrant signalling in response to SCFAs might contribute to symptoms observed in patients with suppressed barrier function.
Topics: Animals; Bicarbonates; Duodenum; Fatty Acids, Volatile; Gastrointestinal Motility; Intestinal Mucosa; Male; Permeability; Rats, Sprague-Dawley
PubMed: 28436589
DOI: 10.1113/EP086110 -
BMJ Case Reports Jan 2019We present a case of a healthy 59-year-old woman who presented for a capsule endoscopy to evaluate melaena and iron deficiency anaemia. She had previously underwent an...
We present a case of a healthy 59-year-old woman who presented for a capsule endoscopy to evaluate melaena and iron deficiency anaemia. She had previously underwent an oesophagogastroduodenoscopy and colonoscopy at an outside institution which were unremarkable. Capsule endoscopy showed an ulcerated, bleeding lesion likely in the duodenum. Differential diagnosis included adenocarcinoma, carcinoid tumour, lymphoma, gastrointestinal stromal tumour and metastatic disease. A push enteroscopy was performed after which showed an ulcerated mass in the third portion of the duodenum. Biopsies confirmed adenocarcinoma. Computed tomography of the abdomen showed no signs of distant metastasis and the patient was referred to surgery for evaluation. The patient underwent a pancreaticoduodenectomy, with resection of the mass and negative lymph nodes in all nine that were removed (T3N0). The patient was classified as stage II duodenal adenocarcinoma. Duodenal adenocarcinoma is a rare but clinically significant cause of small bowel bleeding.
Topics: Adenocarcinoma; Biopsy; Capsule Endoscopy; Diagnosis, Differential; Duodenal Neoplasms; Duodenum; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged
PubMed: 30700455
DOI: 10.1136/bcr-2018-227184