Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis.
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ABSTRACT:
SUBMITTER: van den Berg FF
PROVIDER: S-EPMC8438261 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAcute necrotizing pancreatitis (NP), a severe form of acute pancreatitis (AP), has higher mortality and worse outcome than non-necrotizing pancreatitis (non-NP). Infected NP is a devastating subgroup of NP. To date neither NP nor infected NP has robust prediction strategies, which may delay early recognition and timely intervention. Recent studies revealed correlations between disturbed gut microbiota and AP severity. Some features of intestinal microbiota have the potential to become biomarkers for NP prediction.MethodsWe performed 16S rRNA sequencing to analyze gut microbiota features in 20 healthy controls (HC), and 58 AP patients on hospital admission. The AP patients were later classified into NP and non-NP groups based on subsequent diagnostic imaging features. Random forest regression model and ROC curve were applied for NP and infected NP prediction. PIRCUSt2 was used for bacterial functional pathway prediction analysis.ResultsWe found that the three groups (HC, NP, and non-NP) had distinct microorganism composition. NP patients had reduced microbial diversity, higher abundance of Enterobacteriales, but lower abundance of Clostridiales and Bacteroidales compared with the non-NP group. Correlation analyses displayed that intestine bacterial taxonomic alterations were related to severity, ICU admission, and prognosis. By pathway prediction, species more abundant in NP patients had positive correlation with synthesis and degradation of ketone bodies, and benzoate degradation. Enterococcus faecium (ASV2) performed best in discriminating NP and non-NP patients. Finegoldia magna (ASV3) showed the maximal prediction capacity among all ASVs and had comparable accuracy with Balthazar CT to detect patients with infected NP.ConclusionsOur study suggests that NP patients have distinct intestinal microbiota on admission compared to non-NP patients. Dysbiosis of intestinal microbiota might influence NP progression through ketone body or benzoate metabolism. Enterococcus faecium and Finegoldia magna are potential predictors for NP and infected NP. Our findings explore biomarkers which may inform clinical decision-making in AP and shed light on further studies on NP pathophysiology and management.
| S-EPMC9466706 | biostudies-literature
Project description:BackgroundAcute necrotizing pancreatitis (ANP) can result in a significant healthcare burden. The present study aimed to develop a new scoring system to accurately and promptly identify patients with a high likelihood of mortality to determine the need for aggressive measures.MethodsWe retrospectively analyzed patients diagnosed with ANP using the National Inpatient Sample (NIS). The mortality in ANP during admission (MANP-A) scoring system was derived using multivariate Cox regression analysis and validated using receiver operating characteristic (ROC) curves in a validation cohort.ResultsA total of 22,980 hospitalizations were identified in the derivation cohort. There was a predominance of males (65%) and white race (73%). Five variables showed significant association with mortality and were selected for developing the MANP-A scoring system: age ≥60 years; acute renal failure/kidney injury; sepsis with shock; vasopressor use; and disseminated intravascular coagulation. The MANP-A score has a maximum of 5 points and the cutoff for predicting mortality was set at 2 points. The area under the curve (AUC) using the ROC curve of the derivation cohort was 0.9195, 95% confidence interval [CI] 0.8838-0.9551 (P<0.001) for 7- and 0.8954, 95%CI 0.8723-0.9185 (P<0.001) for 30-day periods. The AUC of the Validation Cohort was 0.9204, 95%CI 0.8937-0.9469 (P<0.001) for 7- and 0.9059, 95%CI 0.8893-0.9223 (P<0.001) for 30-day periods.ConclusionWe propose a simple and objective score for predicting ANP inpatient mortality at 7- and 30-day intervals with high validity.
| S-EPMC9399582 | biostudies-literature
Project description:BackgroundCompared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon.MethodsEighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction.ResultsThe gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not.ConclusionAging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.
| S-EPMC9366017 | biostudies-literature
Project description:The pathophysiology of acute pancreatitis (AP) is not well understood, and the disease does not have specific therapy. Tryptophan metabolite L-kynurenic acid (KYNA) and its synthetic analogue SZR-72 are antagonists of the N-methyl-D-aspartate receptor (NMDAR) and have immune modulatory roles in several inflammatory diseases. Our aims were to investigate the effects of KYNA and SZR-72 on experimental AP and to reveal their possible mode of action. AP was induced by intraperitoneal (i.p.) injection of L-ornithine-HCl (LO) in SPRD rats. Animals were pretreated with 75-300 mg/kg KYNA or SZR-72. Control animals were injected with physiological saline instead of LO, KYNA and/or SZR-72. Laboratory and histological parameters, as well as pancreatic and systemic circulation were measured to evaluate AP severity. Pancreatic heat shock protein-72 and IL-1β were measured by western blot and ELISA, respectively. Pancreatic expression of NMDAR1 was investigated by RT-PCR and immunohistochemistry. Viability of isolated pancreatic acinar cells in response to LO, KYNA, SZR-72 and/or NMDA administration was assessed by propidium-iodide assay. The effects of LO and/or SZR-72 on neutrophil granulocyte function was also studied. Almost all investigated laboratory and histological parameters of AP were significantly reduced by administration of 300 mg/kg KYNA or SZR-72, whereas the 150 mg/kg or 75 mg/kg doses were less or not effective, respectively. The decreased pancreatic microcirculation was also improved in the AP groups treated with 300 mg/kg KYNA or SZR-72. Interestingly, pancreatic heat shock protein-72 expression was significantly increased by administration of SZR-72, KYNA and/or LO. mRNA and protein expression of NMDAR1 was detected in pancreatic tissue. LO treatment caused acinar cell toxicity which was reversed by 250 µM KYNA or SZR-72. Treatment of acini with NMDA (25, 250, 2000 µM) did not influence the effects of KYNA or SZR-72. Moreover, SZR-72 reduced LO-induced H2O2 production of neutrophil granulocytes. KYNA and SZR-72 have dose-dependent protective effects on LO-induced AP or acinar toxicity which seem to be independent of pancreatic NMDA receptors. Furthermore, SZR-72 treatment suppressed AP-induced activation of neutrophil granulocytes. This study suggests that administration of KYNA and its derivative could be beneficial in AP.
| S-EPMC8567016 | biostudies-literature
Project description:Acute necrotizing pancreatitis accounts for 10% of acute pancreatitis (AP) cases and is associated with a higher mortality and morbidity. Necrosis within the first 4 weeks of disease onset is defined as an acute necrotic collection (ANC), while walled off pancreatic necrosis (WOPN) develops after 4 weeks of disease onset. An infected or symptomatic WOPN requires drainage. The management of pancreatic necrosis has shifted away from open necrosectomy, as it is associated with a high morbidity, to less invasive techniques. In this review, we summarize the current management and therapies for acute necrotizing pancreatitis.
| S-EPMC5565044 | biostudies-other
Project description:Polysaccharide is efficient in attenuation of metabolic ailments and modulation of gut microbiota as prebiotics. The therapeutic effect of Inonotus obliquus polysaccharide (IOP) on chronic pancreatitis (CP) in mice has been validated in our previous study. However, it is not clear whether IOP is conducive to maintaining the homeostasis between gut microbiota and host. The aim of this study is to testify the potential effects of IOP on gut microbiota composition and diversity in mice with CP. The changes in glutathione peroxidase (GSH-PX), total antioxidant capacity (TAOC), tumor necrosis factor alpha (TNF-?), transforming growth factor beta (TGF-?), lipase and trypsin levels were measured by commercial assay kits, meanwhile the gut microbiota composition and diversity were analyzed by high throughput sequencing. The IOP treatment increased GSH-PX and TAOC levels, and decreased TNF-?, TGF-?, lipase and trypsin levels in CP mice. It was also observed that gut microbiota in IOP treated groups were less diverse than others in terms of lower Shannon diversity index and Chao 1 estimator. IOP increased the proportion of Bacteroidetes and decreased that of Firmicutes at phylum level. Bacteroidetes was found positively correlated with GSH-PX and TAOC, and Firmicutes correlated with TNF-?, TGF-?, and lipase. In conclusion, administration of IOP could regulate gut microbiota composition and diversity to a healthy profile in mice with CP, and some bacterial phylum significantly correlated with characteristic parameters.
| S-EPMC5309192 | biostudies-literature
Project description:Acute pancreatitis (AP) is usually accompanied by intestinal failure, but its mechanism is still unclear. In AP patients, the functions of Paneth cells (lysozyme, HD5, Reg3γ, and Wnt3a) decreased. Compared with AP mice, injuries and inflammation of the pancreas and ileum were aggravated in AP mice treated with dithizone (Dith) (Dith+AP mice). Intestinal permeability and bacterial translocation were also increased. 16S rRNA sequencing showed that the gut microbiota of Dith mice and Dith+AP mice exhibited a marked increase in the pathogenic bacterium Helicobacter and a significant decrease in the probiotic bacterium Blautia. Lysozyme gavage in Dith+AP mice effectively alleviated injuries of the pancreas and small intestine. The beneficial effect of lysozyme was associated with a significant increase in the probiotic bacterium Blautia and a virtual absence of the pathogenic bacterium Helicobacter. The severity of AP in antibiotic-treated mice (ABX mice) was significantly aggravated when receiving feces from Dith mice and was markedly alleviated when receiving feces from lysozyme-gavaged mice. In vitro, lysozyme increased the proliferation of enteroids by promoting the activation of the Wnt pathway and Lgr5 expression in intestinal stem cells. IMPORTANCE We demonstrate that AP patients and experimental AP mice exhibited a dysfunction of Paneth cells. Our in vivo research showed that the severity of AP was exacerbated by the long-term dysfunction of Paneth cells, which was associated with gut microbiota disorder. Restoring part of Paneth cell functions through lysozyme supplementation alleviated the severity of AP and gut microbiota dysbiosis. This study provides novel insight into the link of pancreas-gut interactions in the pathogenesis of AP, providing a new direction for the clinical treatment of intestinal complications during AP.
| S-EPMC9239092 | biostudies-literature
Project description:Purpose To investigate the dynamic changes in the intestinal microbiota in preterm infants with necrotizing enterocolitis (NEC) before and after treatment via a prospective case-control study. Methods Preterm infants with NEC and preterm infants with similar age and weight (control group) were enrolled in this study. They were divided into NEC_Onset (diagnosis time), NEC_Refeed (refeed time), NEC_FullEn (full enteral nutrition time), Control_Onset, and Control_FullEn groups according to the time of the fecal material collected. Except for basic clinical information, fecal specimens of the infants were obtained as well at indicated times for 16S rRNA gene sequencing. All infants were followed up after discharge from the NICU, and the growth data of the corrected age of 12 months were acquired from the electronic outpatient system and telephonic interviews. Results A total of 13 infants with NEC and 15 control infants were enrolled. A gut microbiota analysis showed that the Shannon and Simpson indices were lower in the NEC_FullEn group than in the Control_FullEn group (p < .05). Methylobacterium, Clostridium_butyricum, and Acidobacteria were more abundant in infants with NEC during diagnosis. Methylobacterium and Acidobacteria were remained plentiful in the NEC group until the end of treatment. These bacteria species were significantly positively correlated with CRP and negatively correlated with platelet count. The rate of delayed growth was higher in the NEC group than in the control group (25% vs. 7.1%) at 12 months of corrected age, but there was no significant difference. In addition, the pathways of synthesis and degradation of ketone bodies were more active in the NEC subgroups, including both the NEC_Onset group and the NEC_FullEn group. The pathway of sphingolipid metabolism was more active in the Control_FullEn group. Conclusion Even after reaching the full enteral nutrition period, alpha diversity in infants with NEC who underwent surgery was lower than that in the control group infants. It may take more time to reestablish the normal gut flora of NEC infants after surgery. The pathways of the synthesis and degradation of ketone bodies and sphingolipid metabolism might be related to the pathogenesis of NEC and physical development after the occurrence of NEC.
| S-EPMC9923499 | biostudies-literature
Project description:BackgroundAbdominal free fluid is frequently encountered on cross-sectional imaging for acute pancreatitis and may be a sign of increased severity and complications. This study examines the ability of free fluid to predict necrotizing pancreatitis and other adverse outcomes.MethodsWe conducted a single-center retrospective study of patients with acute pancreatitis and multiple cross-sectional imaging studies. Patients were divided into those who demonstrated free fluid on initial imaging and those without free fluid. The primary outcome was developing necrotizing pancreatitis. Logistic regression analysis assessed the performance of several predictors.ResultsA total of 245 acute pancreatitis patients were included. Pancreatic necrosis occurred more frequently in the free fluid group (31.3 vs. 1.3%, P<0.001). The free fluid group also had higher rates of transient organ failure (17.7 vs. 3.4%, P<0.001), persistent organ failure (17.7 vs. 2.0%, P<0.001), in-hospital mortality (7.3 vs. 1.3%, P=0.016), length of stay (16.2 vs. 5.5 days, P<0.001), and intensive care unit admission (30.2 vs. 4.7%, P<0.001). On multivariate logistic regression, free fluid was the strongest predictor (adjusted odds ratio 17.11, 95% confidence interval 3.68-79.65; P<0.001) for necrotizing pancreatitis, with an excellent performance (area under the curve 0.92). When neither fluid on initial imaging nor persistent systemic inflammatory response syndrome was present, the negative predictive value for developing pancreatic necrosis was 100%.ConclusionsFree fluid in acute pancreatitis is a strong predictor for necrotizing pancreatitis, organ failure and mortality, and outperformed current predictors. Patients who lacked both free fluid on imaging and persistent systemic inflammatory response syndrome are at low risk for adverse outcomes and may be considered for early discharge.
| S-EPMC8596223 | biostudies-literature
Project description:ObjectivesIntestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP.MethodsRats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence.ResultsANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1β and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme.ConclusionThe disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.
| S-EPMC5404871 | biostudies-literature