The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing
Abstract Background 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 distin...
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-02882-7 |
| _version_ | 1819102542489976832 |
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| author | Wenli Zhou De Zhang Zhengpeng Li Huiqing Jiang Jingnan Li Rongrong Ren Xuefeng Gao Jianfeng Li Xin Wang Weifeng Wang Yunsheng Yang |
| author_facet | Wenli Zhou De Zhang Zhengpeng Li Huiqing Jiang Jingnan Li Rongrong Ren Xuefeng Gao Jianfeng Li Xin Wang Weifeng Wang Yunsheng Yang |
| author_sort | Wenli Zhou |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-22T01:36:13Z |
| format | Article |
| id | doaj.art-9f9425b2ffa5461d9c5b7c220375799c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-22T01:36:13Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-9f9425b2ffa5461d9c5b7c220375799c2022-12-21T18:43:22ZengBMCJournal of Translational Medicine1479-58762021-05-0119111210.1186/s12967-021-02882-7The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencingWenli Zhou0De Zhang1Zhengpeng Li2Huiqing Jiang3Jingnan Li4Rongrong Ren5Xuefeng Gao6Jianfeng Li7Xin Wang8Weifeng Wang9Yunsheng Yang10School of Medicine, Nankai UniversityMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalDepartment of Gastroenterology, The Second Affiliated Hospital of Hebei Medical UniversityDepartment of Gastroenterology, Peking Union HospitalMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalDepartment of Gastroenterology and Hepatology, Shenzhen University General HospitalMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalInstitute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural SciencesMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalMicriobiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General HospitalAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12967-021-02882-7Pancreatic ductal adenocarcinomaAutoimmune pancreatitisFecal microbiotaMetagenomic sequencingButyrate |
| spellingShingle | Wenli Zhou De Zhang Zhengpeng Li Huiqing Jiang Jingnan Li Rongrong Ren Xuefeng Gao Jianfeng Li Xin Wang Weifeng Wang Yunsheng Yang The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing Journal of Translational Medicine Pancreatic ductal adenocarcinoma Autoimmune pancreatitis Fecal microbiota Metagenomic sequencing Butyrate |
| title | The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| title_full | The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| title_fullStr | The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| title_full_unstemmed | The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| title_short | The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| title_sort | fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing |
| topic | Pancreatic ductal adenocarcinoma Autoimmune pancreatitis Fecal microbiota Metagenomic sequencing Butyrate |
| url | https://doi.org/10.1186/s12967-021-02882-7 |
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