Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development

Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples; preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.

[1]  J. Szabó,et al.  Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma , 2020, Cancers.

[2]  Yanhong Gu,et al.  The potential role of bacteria in pancreatic cancer: A systematic review. , 2020, Carcinogenesis.

[3]  Fiona Ginty,et al.  The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View , 2020, Trends in cancer.

[4]  Jianguo Xia,et al.  Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data , 2020, Nature Protocols.

[5]  B. Helmink,et al.  The Tumor Microbiome in Pancreatic Cancer: Bacteria and Beyond. , 2019, Cancer cell.

[6]  C. Jobin,et al.  Microbiota in pancreatic health and disease: the next frontier in microbiome research , 2019, Nature Reviews Gastroenterology & Hepatology.

[7]  U. Gophna,et al.  Fecal microbiome signatures of pancreatic cancer patients , 2019, Scientific Reports.

[8]  A. Kramer,et al.  Bacterobilia in pancreatic surgery-conclusions for perioperative antibiotic prophylaxis , 2019, World journal of gastroenterology.

[9]  Wei-Fang Zhu,et al.  Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer , 2019, World journal of gastrointestinal oncology.

[10]  R. Grützmann,et al.  The impact of surgical experience and frequency of practice on perioperative outcomes in pancreatic surgery , 2019, BMC Surgery.

[11]  Christine B. Peterson,et al.  Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes , 2019, Cell.

[12]  W. Lieb,et al.  Alterations of the bile microbiome in primary sclerosing cholangitis , 2019, Gut.

[13]  E. Elinav,et al.  The cancer microbiome , 2019, Nature Reviews Cancer.

[14]  Xianjun Yu,et al.  The microbiota and microbiome in pancreatic cancer: more influential than expected , 2019, Molecular Cancer.

[15]  Paul Theodor Pyl,et al.  Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer , 2019, Nature Medicine.

[16]  M. Weigand,et al.  Gut microbiome patterns correlate with higher postoperative complication rates after pancreatic surgery , 2019, BMC Microbiology.

[17]  A. Zaborin,et al.  Novel de novo synthesized phosphate carrier compound ABA‐PEG20k‐Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model , 2018, The British journal of surgery.

[18]  C. Fitzmaurice.  Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 2006 to 2016: A systematic analysis for the Global Burden of Disease study. , 2018 .

[19]  B. Helmink,et al.  The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. , 2018, Cancer cell.

[20]  S. Pushalkar,et al.  The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. , 2018, Cancer discovery.

[21]  M. Arumugam,et al.  Circulating microbiome in blood of different circulatory compartments , 2018, Gut.

[22]  J. Matthews.  Infection After Pancreatic Surgery: Superficial and Deep Thoughts. , 2017, JAMA surgery.

[23]  P. Auvinen,et al.  Bile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia , 2017, PloS one.

[24]  Jasmine Chong,et al.  MicrobiomeAnalyst: a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data , 2017, Nucleic Acids Res..

[25]  Alan D. Lopez,et al.  Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study , 2017, JAMA oncology.

[26]  T. Keck,et al.  Quality Indicators in Pancreatic Surgery: Lessons Learned from the German DGAV StuDoQ|Pancreas Registry , 2017, Visceral Medicine.

[27]  Robert C. Edgar,et al.  SINTAX: a simple non-Bayesian taxonomy classifier for 16S and ITS sequences , 2016, bioRxiv.

[28]  T. Conroy,et al.  Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[29]  James N. Luo,et al.  Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak , 2015, Science Translational Medicine.

[30]  K. Theodoraki,et al.  Erratum to: Preoperative Biliary Drainage of Severely Jaundiced Patients Increases Morbidity of Pancreaticoduodenectomy: Results of a Case-Control Study , 2014, World Journal of Surgery.

[31]  P. Gajer,et al.  An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform , 2014, Microbiome.

[32]  Robert C. Edgar,et al.  UPARSE: highly accurate OTU sequences from microbial amplicon reads , 2013, Nature Methods.

[33]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[34]  Marcel Martin.  Cutadapt removes adapter sequences from high-throughput sequencing reads , 2011 .

[35]  M. Callery,et al.  Risk Prediction for Development of Pancreatic Fistula Using the ISGPF Classification Scheme , 2008, World Journal of Surgery.

[36]  S. Rushbrook,et al.  Human bile retrieved from the normal biliary system is not sterile , 2017 .

[37]  K. Theodoraki,et al.  Preoperative Biliary Drainage of Severely Jaundiced Patients Increases Morbidity of Pancreaticoduodenectomy: Results of a Case-Control Study , 2014, World Journal of Surgery.

[38]  M. Callery,et al.  A Multi-Institutional External Validation of the Fistula Risk Score for Pancreatoduodenectomy , 2013, Journal of Gastrointestinal Surgery.

[39]  T. Kent,et al.  A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. , 2013, Journal of the American College of Surgeons.

[40]  Robert C. Edgar,et al.  Search and clustering orders of magnitude faster than BLAST , 2010 .