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The American Journal of Gastroenterology Jun 2024Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects...
INTRODUCTION
Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity.
METHODS
Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed.
RESULTS
Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias.
DISCUSSION
Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.
Topics: Humans; Obesity; Female; Male; Overweight; Middle Aged; Gastrointestinal Microbiome; Adult; Duodenum; RNA, Ribosomal, 16S; Biomarkers; Lactobacillus; Bifidobacterium; Aged
PubMed: 38578969
DOI: 10.14309/ajg.0000000000002790 -
World Journal of Gastroenterology Sep 2020There are few reports on major gastrointestinal (GI) bleeding among patients receiving an antithrombotic.
BACKGROUND
There are few reports on major gastrointestinal (GI) bleeding among patients receiving an antithrombotic.
AIM
To describe clinical characteristics, bleeding locations, management and in-hospital mortality related to these events.
METHODS
Over a three-year period, we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1, 2013 and December 31, 2015 for major GI bleeding while receiving an antithrombotic. The bleeding events were medically validated. Clinical characteristics, causative lesions, management and fatalities were described. The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.
RESULTS
Of 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding. No cause was identified for 383 (35.5%) patients. Gastro-duodenal ulcer was the first causative lesion in the upper tract (209 out of 408) and colonic diverticulum the first causative lesion in the lower tract (120 out of 289). There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations ( = 0.03). There was an independent association between gastro-duodenal ulcer and antithrombotic use ( = 0.03), taking account of confounders and proton pump inhibitor co-prescription. Pair wise comparisons pointed to a difference between vitamin K antagonist, direct oral anticoagulants, and antiplatelet agents in monotherapy dual antiplatelet agents.
CONCLUSION
We showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding. Management was similar across antithrombotics and in-hospital mortality was low (5.95%).
Topics: Adult; Anticoagulants; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Peptic Ulcer; Platelet Aggregation Inhibitors
PubMed: 33024397
DOI: 10.3748/wjg.v26.i36.5463 -
Medicine Nov 2021The similarities and differences between acute esophageal necrosis and severe reflux esophagitis have not been elucidated. We compared Los Angeles classification Grade C... (Observational Study)
Observational Study
The similarities and differences between acute esophageal necrosis and severe reflux esophagitis have not been elucidated. We compared Los Angeles classification Grade C reflux esophagitis, Grade D reflux esophagitis, and acute esophageal necrosis to consider the similarities and differences between acute esophageal necrosis and severe reflux esophagitis.We retrospectively reviewed records of patients who underwent esophagogastroduodenoscopy at a tertiary referral center from January 2012 to December 2019. Data on patients diagnosed as Grade C reflux, Grade D reflux, or acute esophageal necrosis for the first time were extracted for analysis.A total of 213 patients were enrolled in the study, composed of 130 Grade C reflux, 74 Grade D reflux, and 9 acute esophageal necrosis patients. Compared to Grade C reflux patients, Grade D reflux and acute esophageal necrosis patients were more likely to be transfused (P = .013 and P = .011, respectively), to have duodenal ulcers (P = .025 and P = .049, respectively), and to have psychiatric illnesses (P = .022 and P = .018, respectively). Compared to both Grade C and D reflux, acute esophageal necrosis patients were more likely to present with shock (P = .003 and P < .001, respectively), have type 1 diabetes (P = .030 and P = .004, respectively), and present in winter (P < .001 and P < .001, respectively). Significant step-wise differences (Grade C < Grade D < acute esophageal necrosis) were observed in the need for admission (P < .001 and P = .009), coffee ground emesis (P < .001 and P = .022), and stigmata of hemorrhage on endoscopy (P = .002 and P < .001). Admission (P = .003) and coffee ground emesis (P = .003) independently predicted either Grade D reflux or acute esophageal necrosis over Grade C reflux on multivariate analysis.Shock, type 1 diabetes, and winter may predict acute esophageal necrosis, while the need for admission and coffee ground emesis may predict Grade D reflux or acute esophageal necrosis.
Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 1; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Hematemesis; Humans; Hyperplasia; Male; Middle Aged; Necrosis; Retrospective Studies
PubMed: 34871245
DOI: 10.1097/MD.0000000000027672 -
Journal of Clinical Immunology Feb 2023About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology...
PURPOSE
About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute.
METHODS
Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNA-sequencing, and RT-qPCR of genes of interest.
RESULTS
VA development was connected to the lack of intestinal (IgA) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzymeCD8 T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type I/III and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA) PCs. Chronic NV infection exacerbated this signature when compared to stage-matched NV-negative samples.
CONCLUSIONS
Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.
Topics: Humans; Atrophy; Caliciviridae Infections; CD8-Positive T-Lymphocytes; Common Variable Immunodeficiency; Immunoglobulin A; Inflammation; Interferons; Norovirus
PubMed: 36282455
DOI: 10.1007/s10875-022-01379-2 -
Global Pediatric Health 2023Conservative treatment of duodenal trauma in children has long been the first line of treatment for duodenal wall hematomas. However, it has rarely been described in...
Conservative treatment of duodenal trauma in children has long been the first line of treatment for duodenal wall hematomas. However, it has rarely been described in duodenal perforations. Our purpose is to highlight the possibility of conservative treatment in selected cases of duodenal perforation. In the period between 2009 and 2022, 6 children were treated for duodenal injury following abdominal blunt trauma in the pediatric surgical emergency department. The clinical presentation, diagnosis and treatment are reported and analyzed. Three patients presented with duodenal hematomas, they were treated non-operatively with hospital stays between 12 and 20 days and good clinical outcome. One child presented with duodenal hematoma and retroperitoneal air bubbles; non-operative conservative treatment was carried with favorable results. The fifth patient had a duodenal perforation; he underwent a primary duodenal 2-layers closure. The last patient had a combination of duodenal hematoma and perforation involving 75% of the duodenal diameter for which he underwent a gastro-jejunostomy with pyloric exclusion. An isolated duodenal lesion can be subject to a conservative treatment whenever allowed by a stable clinical condition and the availability of appropriate clinical and radiological monitoring.
PubMed: 36992845
DOI: 10.1177/2333794X231156057 -
Journal of Veterinary Diagnostic... Mar 2020Focal duodenal necrosis (FDN) is an intestinal disease of egg-layer chickens characterized by multifocal necrosis of the duodenal loop and proximal jejunum. Affected...
Focal duodenal necrosis (FDN) is an intestinal disease of egg-layer chickens characterized by multifocal necrosis of the duodenal loop and proximal jejunum. Affected flocks usually have decreased egg weights and drops in egg production. Previous studies have associated this condition with infection. We tried to reproduce FDN by experimental infection of egg-laying chickens using different -positive and -negative strains, and duodenal homogenate obtained from FDN lesions. Chickens challenged with and/or duodenal homogenate developed duodenitis after challenge. Gross lesions included mucosal erosions, hyperemia, mucosal hemorrhages, and watery intestinal content. Microscopic lesions included mild enterocyte degeneration and necrosis, and mild-to-moderate hemorrhage and lymphoplasmacytic and heterophilic infiltration of the lamina propria. Two -positive strains closely related to necrotic enteritis pathogenic strains, by genomic composition, were re-isolated from lesions. Necrosis of intestinal crypts was observed in chickens challenged with duodenal homogenate with or without coinfection. Characteristic microscopic FDN lesions with significant necrosis and loss of villus enterocytes were not reproduced.
Topics: Animals; Chickens; Clostridium Infections; Clostridium perfringens; Duodenum; Enteritis; Poultry Diseases; Stomach Diseases
PubMed: 31983302
DOI: 10.1177/1040638720901726 -
Haematologica Aug 2021Clinical studies suggested that endothelial dysfunction and damage could be involved in the development and severity of acute graft-versus-host disease (aGVHD)....
Clinical studies suggested that endothelial dysfunction and damage could be involved in the development and severity of acute graft-versus-host disease (aGVHD). Accordingly, we found increased percentage of apoptotic Casp3+ blood vessels in duodenal and colonic mucosa biopsies of patients with severe aGVHD. In murine experimental aGVHD, we detected severe microstructural endothelial damage and reduced endothelial pericyte coverage accompanied by reduced expression of endothelial tight junction proteins leading to increased endothelial leakage in aGVHD target organs. During intestinal aGVHD, colonic vasculature structurally changed, reflected by increased vessel branching and vessel diameter. Because recent data demonstrated an association of endothelium-related factors and steroid refractory aGVHD (SR-aGVHD), we analyzed human biopsies and murine tissues from SR-aGVHD. We found extensive tissue damage but low levels of alloreactive T cell infiltration in target organs, providing the rationale for T-cell independent SR-aGVHD treatment strategies. Consequently, we tested the endothelium-protective PDE5 inhibitor sildenafil, which reduced apoptosis and improved metabolic activity of endothelial cells in vitro. Accordingly, sildenafil treatment improved survival and reduced target organ damage during experimental SR-aGVHD. Our results demonstrate extensive damage, structural changes, and dysfunction of the vasculature during aGVHD. Therapeutic intervention by endothelium-protecting agents is an attractive approach for SR-aGVHD complementing current anti-inflammatory treatment options.
Topics: Animals; Endothelial Cells; Endothelium; Graft vs Host Disease; Humans; Mice; Steroids; T-Lymphocytes
PubMed: 32675225
DOI: 10.3324/haematol.2020.253716 -
Nature Communications Jul 2022The small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from...
The small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from the early 1970s uncovered unusual spatial organization of small intestinal villus tip blood vessels: their exterior, epithelial-facing side is fenestrated, while the side facing the villus stroma is non-fenestrated, covered by pericytes and harbors endothelial nuclei. Such organization optimizes the absorption process, however the molecular mechanisms maintaining this highly specialized structure remain unclear. Here we report that perivascular LGR5 villus tip telocytes (VTTs) are necessary for maintenance of villus tip endothelial cell polarization and fenestration by sequestering VEGFA signaling. Mechanistically, unique VTT expression of the protease ADAMTS18 is necessary for VEGFA signaling sequestration through limiting fibronectin accumulation. Therefore, we propose a model in which LGR5 ADAMTS18 telocytes are necessary to maintain a "just-right" level and location of VEGFA signaling in intestinal villus blood vasculature to ensure on one hand the presence of sufficient endothelial fenestrae, while avoiding excessive leakiness of the vessels and destabilization of villus tip epithelial structures.
Topics: Duodenum; Intestinal Mucosa; Intestines; Nutrients; Telocytes
PubMed: 35810168
DOI: 10.1038/s41467-022-31571-2 -
Pancreas Jul 2021Gastrointestinal bleeding (GIB) is an uncommon complication after abdominal surgery. Given the unique risks in the total pancreatectomy with islet autotransplant (TPIAT)...
OBJECTIVE
Gastrointestinal bleeding (GIB) is an uncommon complication after abdominal surgery. Given the unique risks in the total pancreatectomy with islet autotransplant (TPIAT) population, we aimed to describe this population's incidence of postoperative GIB.
METHODS
Prospectively collected data on patients who underwent a TPIAT from 2001 to 2018 at the University of Minnesota were reviewed for postoperative GIB. Each GIB patient was matched to a control patient and compared for medical, medication, and social history and for clinical outcomes.
RESULTS
Sixty-eight patients developed a GIB (12.4%) at median time after surgery of 17 months. Etiologies included the following: anastomotic ulcer (35%), Clostridium difficile (4%), gastric or duodenal ulcers (9%), esophagitis/gastritis (10%), hemorrhoids (3%), inflammatory bowel disease (4%), Mallory-Weiss tears (1%), and unknown (29%). During diagnostic workup, 87% had an endoscopic procedure and 3% underwent imaging. Seven patients required an operation (10%), 1 required an open embolization (1%), and 13 required endoscopic treatments (19%). Patients with a GIB were more likely to die (15% vs 5%, P = 0.055).
CONCLUSIONS
Twelve percent of patients developed a GIB after TPIAT. One third of those had an undefined etiology despite endoscopy. The need for intervention was high (30%).
Topics: Adult; Female; Gastrointestinal Hemorrhage; Humans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Postoperative Complications; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; Transplantation, Autologous; Young Adult
PubMed: 34347732
DOI: 10.1097/MPA.0000000000001842 -
BMC Surgery Jun 2021En bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided...
BACKGROUND
En bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer with duodenal invasion. Information regarding the indications and outcomes of this procedure is limited.
METHOD
In this retrospective study, 2269 patients with right colon cancer underwent radical right colectomy between October 2010 and May 2019, in which 19 patients underwent RHCPD for LARCC were identified. The overall survival (OS), disease-free survival (DFS), operative mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan-Meir method.
RESULTS
Of these 19 patients who underwent LARCC, the OS was 88%, 66%, and 58% at 1, 3, and 5 years. The DFS was 72%, 56%, and 56% at 1, 3, and 5 years. The median operative time was 320 min (range: 222-410 min), and the median operative blood loss was 268 mL (range: 100-600 mL). The OS was significantly better among patients with well-differentiated tumor, N0 stage, and high microsatellite instability (MSI) and in patients who received adjuvant chemotherapy. The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P < 0.05).
CONCLUSIONS
This study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.
Topics: Colectomy; Colonic Neoplasms; Duodenum; Humans; Pancreaticoduodenectomy; Retrospective Studies
PubMed: 34187443
DOI: 10.1186/s12893-021-01286-0