Abstract
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.
Highlights
Pancreatic cancer is one of the most common cause of cancer death and leads to an estimated 227,000 deaths annually worldwide [1], and more than 80% of the pancreatic malignancy are the pancreatic ductal adenocarcinomas (PDAC)
autoimmune pancreatitis (AIP) is mostly accompanied by an expanded pancreas; AIP remains challenging to diagnose at an early stage or to distinguish between PDAC and AIP patients via imaging, which can result in unnecessary surgical resection when PDAC is suspected [5]
The results revealed that axis 2 discriminated most of the healthy controls (HCs) samples from most of the PDAC samples (PERMANOVA, p = 0.001)
Summary
Pancreatic cancer is one of the most common cause of cancer death and leads to an estimated 227,000 deaths annually worldwide [1], and more than 80% of the pancreatic malignancy are the pancreatic ductal adenocarcinomas (PDAC). The pathogenesis, the new diagnostic strategies and preventive therapeutic means must be explored for PDAC. The AIP and IgG4-related disease pathogeneses are largely unknown. AIP is mostly accompanied by an expanded pancreas; AIP remains challenging to diagnose at an early stage or to distinguish between PDAC and AIP patients via imaging, which can result in unnecessary surgical resection when PDAC is suspected [5]. 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
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