Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders

Background/Aims@#To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. @*Methods@#Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). @*Results@#Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett’s esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES (P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). @*Conclusions@#Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.

Endoscopy in the diagnosis and management of esophageal motility disorders / 中华胃肠外科杂志

With the development of optics and mechanics, endoscopic technologies are not only used as a simple diagnostic method, but also applied in therapy. Since the beginning of the 21st century, minimally invasive medicine has become the development trend. Many novel technologies have appeared, such as endoscopic mucosal resection, endoscopic submucosal dissection, and peroral endoscopic myotomy. Esophageal motility disorders are common diseases in clinic, which seriously affect the quality of life. Although esophageal manometry is the golden diagnostic standard, endoscopy also plays an important role in diagnosis. There are many therapeutic methods in achalasia and gastroesophageal reflux diseases with good efficacy, while the therapy in other esophageal motility disorders remains in dispute. According to the domestic and foreign research progressions, we introduce the role of endoscopy in the diagnosis and management of esophageal motility disorders.

Esophageal motility in patients with sliding hiatal hernia with reflux esophagitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with sliding hiatus hernia (HH) and reflux esophagitis (RE) usually suffer from esophageal dysmotility. The aim of the present study was to investigate the role of acid reflux and duodenal gastroesophageal reflux (DGER), esophageal manometry, and esophageal dysmotility by applying the barium meal examination.</p><p><b>METHODS</b>RE with HH was initially diagnosed using the reflux disease questionnaire, and was further confirmed by a barium meal examination and an endoscopy. The radiographic technique was used to test for spasms, strictures, and the coarseness of the mucosa, also was to study the types of reflux and clearance. Then, the esophageal manometry, the esophageal 24-hour pH, and the bilirubin monitoring were observed.</p><p><b>RESULTS</b>Fifty-five patients were diagnosed as HH combined with RE and divided into two groups according to the severity of their esophagitis: group HH1 (grades A and B) and group HH2 (grades C and D). The barium meal examination revealed that the mucosa was either granular or nodular in all cases. The dump reflux and delayed clearance were more significant in patients in the HH2 group than those in the HH1 group (P < 0.05). The percentages of total, supine, and upright acid exposure time were greater in patients with HH than those in the control group (P < 0.01), but the differences between the HH1 and the HH2 groups were not significant. Lower esophageal sphincter pressure (LESP) was lower in the HH group than in the control group (P < 0.05). Three DGER parameters: the percentage of time with absorbance greater than 0.14, the number of bile reflux episodes, the number of bile refluxes lasting longer than 5 minutes were (28.43 +/- 23.34), (40.57 +/- 31.30), and (15.15 +/- 8.72), respectively in the HH2 group; these statistics were significantly higher than those for the HH1 (P < 0.05). The frequency and amplitude of peristalsis were all lower in HH patients than in the control (P < 0.05). Of all the patients, 54.3% (30 of 55) with acid reflux and DGER simultaneously in the HH group exhibited refluxes of barium from the stomach to the esophagus in the recumbent position, and 29.4% (5 in 17) with delayed clearance in the HH group were correlated with esophageal body peristalses. The result was that the frequency and amplitude of peristalsis were less and the duration of esophageal peristalsis was longer than those of control group.</p><p><b>CONCLUSIONS</b>Esophageal dysmotility may play an important role in the severity of RE combined with HH. Esophageal motility results on a barium examination may coincide with esophageal manometry, 24-hour pH, and bilirubin monitoring in the RE and HH, but the radiologic method was the simplest to apply.</p>

Analysis of esophageal sensation in patients with non-erosive reflux disease / 中华消化杂志

Objective To investigate esophageal response to intraesophageal balloon-distention and acid perfusion stimuli and to evaluate the visceral hypersensitivity in non erosive reflux disease (NERD) patients.Methods Thirty-one NERD patients diagnosed by reflux disease questionnaire (RDQ) and endoscopy and 10 control subjects were enrolled in this study.Esophageal mechanical sensitivity was measured by esophageal barostat and recorded as initial perception threshold and maximal tolerated pain threshold by volume.The chemical sensitivity was measured by acid perfusion test,and quantified by two parameters (trigger time and acid related symptom score).Results Initial perception threshold and maximally tolerated pain threshold of NERD patients was (9.6?4.8) ml and (12.3?3.2) ml, significantly lower than those of controls,(13.2?7.5) ml and (21.6?5.7) ml,respectively (P

Aberrant methylation of CpG island in 5′promoter region of p16 gene and its role in diagnosis of pancreatic cancer / 第二军医大学学报

Objective:To investigate the aberrant methylation of CpG island in 5′promoter region of p16 gene in the pancreatic juice and its value in diagnosis of patients with pancreatic cancer.Methods:Pure pancreatic juice(PPJ)was collected from the pancreatic duct by a nasopancreatic tube put under endoscopic retrograde cholangiopancreatography(ERCP). Cytological examination was performed by H-E staining in pure pancreatic juice.Aberrant p16 methylation was detected using the methylation specific PCR(MSP)in the PPJ.Results:The sensitivity,specificity,positive predictive value,negative predictive value and accuracy cytological examination in diagnosis of pancreatic cancer were 40%,100%,100%,45.4% and 60.0%,respectively.The DNA sequences were successfully extracted from the PPJ of 30 patients with pancreatic diseases and were subjected to MSP.Seven(35%)of the 20 cases with pancreatic cancer showed aberrant methylation of p16 gene.No aberrant methylation was detected in the pancreatic juice samples of patients with chronic pancreatitis and mucinous cystoadenocarcinoma of pancreas.When cytological examination combined with p16 methylation detection,the sensitivity, specificity,positive predictive value,negative predictive value and accuracy for diagnosis of pancreatic cancer were 55%,100%, 100%,52.6% and 70%,respectively.Conclusion:Pancreatic juice collected by nasopancreatic drainage during ERCP can be used for molecular analysis.Detection of aberrant methylation of p16 gene in pancreatic juice combined with cytological examination is a better method for diagnosis of pancreatic cancer.