The Microbiomes of Pancreatic and Duodenum Tissue Overlap and Are Highly Subject Specific but Differ between Pancreatic Cancer and Noncancer Subjects

Abstract

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals. Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples. Results: Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects. Conclusions: Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined. Impact: Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.

Oral microbial community composition is associated with pancreatic cancer: A case‐control study in Iran

“…One study found that individuals who had pancreatic tissue sampled after foregut surgery had a higher prevalence of Kluyvera (genus within the Enterobacteriaceae family) compared to pancreatic tissue from deceased controls; however, when comparing pancreatic cancer tissue to deceased control pancreatic tissue, Salmonella , Enterobacter , and Raoultella (genera within the Enterobacteriaceae family) had a lower prevalence. Similar to our results, this study also found a higher prevalence of Bacteroides (genus within the Bacteroidaceae family) in pancreatic cancer tissue compared to deceased control pancreatic tissue …”

Pancreatic Cancer, Gut Microbiota, and Therapeutic Efficacy

“…Geller et al [29] reported that 15% (3/20) of normal pancreatic tissues contain bacterial DNA via qPCR detection. In both PDAC and noncancer patients, similar bacterial profiles were detected at different sites of the pancreas and duodenum tissues within the same individual, suggesting that intrapancreatic bacteria may migrate from the surrounding gut tract across the intestinal wall [72].…”

“…The Fusobacterium species, a group of oral bacteria, were initially detected in PDAC tissues by Mitsuhashi et al [78] and were found to be independently associated with a worse patient survival probability. The intrapancreatic abundance of Fusobacterium species was found to be relatively higher in PDAC subjects than in noncancer controls [72]. Fusobacterium nucleatum elicited chemoresistance to 5-FU and oxaliplatin in CRC, targeting TLR4 and MyD88 immune signaling and activating the cancer autophagy pathway via downregulation of miR-18a* and miR-4802 [30].…”

A Bayesian framework for identifying consistent patterns of microbial abundance between body sites

“…In their review, Goodman and Gardner (2018) summarize several compelling examples, such as increased Fusobacterium species associating with tumors in colon and Helicobacter pylori inducing lymphoma and gastric cancer. More recently, bacteria have been identified in pancreatic tissue in cancer patients (del Castillo et al, 2019) and have been shown to play a role in carcinogenesis in the pancreas (Pushalkar et al, 2018). Additional studies have also reported evidence that certain oral bacteria and periodontal disease associate with an increased risk in pancreatic cancer (Michaud et al, 2012;Fan et al, 2016).…”