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

Abstract

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.

Liquid biopsies and cancer omics

“…Stool in particular have been thoroughly evaluated in the context of gastrointestinal cancers, and proved to be a valuable source of tumoral DNA for pancreatic cancer [37][38][39][40] . Stool analysis from a multiomics perspective is also able to integrate information on the role of the microbiome in cancer pathogenesis, especially in the case of colorectal cancer and pancreatic cancer, as well as in other disease entities such as inflammatory intestinal diseases [41][42][43] . The microbiota creates a complex network that can influence the tumor microenvironment in a very heterogeneous way that relies on the intrinsically heterogeneity of the microbiome itself [44][45][46][47][48][49] .…”

The Role of Targeted Versus Standard Antibiotic Prophylaxis in Pancreatoduodenectomy in Reducing Postoperative Infectious Complications

“…These findings may have greater implications than just reducing SSI rates, as Sano and colleagues have also found that Enterococcus species detected in organ/space SSI fluid is associated with a trend toward higher incidence of clinically relevant postoperative pancreatic fistulae (86% vs 36%, P ¼ 0.066), 34 which is consistent with findings reported in previous studies. [52][53][54][55] These findings suggest that current antibiotic recommendations by the CDC guidelines are insufficient for antibiotic prophylaxis in PD and that these specific bacterial species should be covered when considering the choice of prophylactic antibiotics. Thus, broad-spectrum antibiotics such as piperacillin/tazobactam, or ampicillin/clavulanic acid should be considered as options for safe and effective prophylaxis.…”

A Comprehensive Review of the Current and Future Role of the Microbiome in Pancreatic Ductal Adenocarcinoma

“…There is likely a relationship between duodenum, gut, and pancreatic tumour microbiomes; however, the route(s) underlying colonisation of the pancreas remain debated [ 13 , 37 ]. A growing body of evidence suggests that one such route is translocation from the gut, specifically from the duodenum retrograde up the bile and pancreatic ducts, thereby, allowing colonisation of the pancreatic microenvironment [ 13 , 21 , 32 , 34 , 38 ].…”

“…If the constituents of the gut microbiome can affect the colonisation of the PDAC tissue [ 21 , 32 , 34 , 38 ], we must ponder altering gut microbiome in order to modify the tumour microbiome. It has been shown that microbiota from human faecal microbial transplants (FMT) administered to murine PDAC models can be detected in the PDAC microbiome post transplantation, albeit in small quantities of less than 5% [ 16 ].…”