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WebPage:
      mainEntity:
         headline:The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing
         description:The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP. 32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method. Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47–100%), 88.89% (95% CI 73.49–100%), and 76.54% (95% CI 52.5–100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively. In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.
         datePublished:2021-05-18T00:00:00Z
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            Pancreatic ductal adenocarcinoma
            Autoimmune pancreatitis
            Fecal microbiota
            Metagenomic sequencing
            Butyrate
            Biomedicine
            general
            Medicine/Public Health
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      headline:The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing
      description:The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP. 32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method. Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47–100%), 88.89% (95% CI 73.49–100%), and 76.54% (95% CI 52.5–100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively. In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.
      datePublished:2021-05-18T00:00:00Z
      dateModified:2021-05-18T00:00:00Z
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      pageEnd:12
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12967-021-02882-7
      keywords:
         Pancreatic ductal adenocarcinoma
         Autoimmune pancreatitis
         Fecal microbiota
         Metagenomic sequencing
         Butyrate
         Biomedicine
         general
         Medicine/Public Health
      image:
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      name:Zhengpeng Li
      affiliation:
            name:The First Medical Center, Chinese PLA General Hospital
            address:
               name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Zhejiang Academy of Agricultural Sciences
            address:
               name:Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
               type:PostalAddress
            type:Organization
      name:Huiqing Jiang
      affiliation:
            name:The Second Affiliated Hospital of Hebei Medical University
            address:
               name:Department of Gastroenterology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
               type:PostalAddress
            type:Organization
      name:Jingnan Li
      affiliation:
            name:Peking Union Hospital
            address:
               name:Department of Gastroenterology, Peking Union Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Rongrong Ren
      affiliation:
            name:The First Medical Center, Chinese PLA General Hospital
            address:
               name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xuefeng Gao
      affiliation:
            name:Shenzhen University General Hospital
            address:
               name:Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, China
               type:PostalAddress
            type:Organization
            name:Shenzhen University
            address:
               name:Clinical Medical Academy, Shenzhen University, Shenzhen, China
               type:PostalAddress
            type:Organization
      name:Jianfeng Li
      affiliation:
            name:The First Medical Center, Chinese PLA General Hospital
            address:
               name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Chinese PLA General Hospital
            address:
               name:School of Medicine, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xin Wang
      affiliation:
            name:Zhejiang Academy of Agricultural Sciences
            address:
               name:Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
               type:PostalAddress
            type:Organization
      name:Weifeng Wang
      affiliation:
            name:The First Medical Center, Chinese PLA General Hospital
            address:
               name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Yunsheng Yang
      affiliation:
            name:The First Medical Center, Chinese PLA General Hospital
            address:
               name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital
            address:
               name:National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:School of Medicine, Nankai University, Tianjin, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:School of Medicine, Chinese PLA General Hospital, Beijing, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:School of Medicine, Chinese PLA General Hospital, Beijing, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
      name:Department of Gastroenterology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
      name:Department of Gastroenterology, Peking Union Hospital, Beijing, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, China
      name:Clinical Medical Academy, Shenzhen University, Shenzhen, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:School of Medicine, Chinese PLA General Hospital, Beijing, China
      name:Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
      name:National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

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