Analysis of the fecal metagenome in long-term survivors of pancreas cancer |
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| Authors: | Jordan Kharofa MD David Haslam MD Rachael Wilkinson MS Allison Weiss PhD Sameer Patel MD Kyle Wang MD Hope Esslinger MPT CCRC Olugbenga Olowokure MD Davendra Sohal MD Greg Wilson MD Syed Ahmad MD Senu Apewokin MD |
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| Institution: | 1. Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;2. Microbial Metagenomics Analysis Center at Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA;3. Department of Infectious Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;4. Department of Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;5. Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;6. Department of Hematology/Oncology Division, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA |
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| Abstract: | Background The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described. Methods In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls. Results All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4–14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia muciniphila species. Conclusions Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa. Plain Language Summary - Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%.
- Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system.
- In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls.
- Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia muciniphila.
- These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.
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| Keywords: | Akkermansia muciniphila Faecalibacterium prausnitzii long-term survivor Malassezia metagenomics microbiome pancreatic cancer |
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