The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing

Journal of Translational Medicine

Xuefeng Gao¹  Jingnan Li²  Huiqing Jiang³  Xin Wang⁴  Rongrong Ren⁵  Weifeng Wang⁵  Zhengpeng Li⁶  Yunsheng Yang⁷  Jianfeng Li⁸  De Zhang⁸  Wenli Zhou⁹ 

[1] Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, 518055, Shenzhen, China;Clinical Medical Academy, Shenzhen University, 518060, Shenzhen, China;Department of Gastroenterology, Peking Union Hospital, 100005, Beijing, China;Department of Gastroenterology, The Second Affiliated Hospital of Hebei Medical University, 050000, Shijiazhuang, China;Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, 310021, Hangzhou, China;Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China;Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China;Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, 310021, Hangzhou, China;Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China;National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 100853, Beijing, China;Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China;School of Medicine, Chinese PLA General Hospital, 100853, Beijing, China;School of Medicine, Nankai University, 300190, Tianjin, China;Micriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China;School of Medicine, Chinese PLA General Hospital, 100853, Beijing, China;

关键词: Pancreatic ductal adenocarcinoma;    Autoimmune pancreatitis;    Fecal microbiota;    Metagenomic sequencing;    Butyrate;   

DOI  :  10.1186/s12967-021-02882-7

来源: Springer

【 摘 要 】

BackgroundThe 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.Methods32 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.ResultsPrincipal 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.ConclusionsIn 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.

【 授权许可】

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