Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy

Abstract

Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.

Microbial profile in bile from pancreatic and extra-pancreatic biliary tract cancer

“…Comparing pancreatic and extra-pancreatic malignancy disease, we found that Alcaligenes faecalis was more correlated to extra-pancreatic cancers (EPC). Conversely, bacteria such as Morganella morganii and Pantoea agglomerans that have been shown to prevent excessive bacterial translocation and inflammation were significantly less frequent in pancreatic cancer patients [ 15 , 30 ].…”

“…Studies on bile samples for microbiological analysis and to collect research data on the microbiota in patients with pancreas and biliary tract cancer are emerging [9][10][11][12][13][14][15]. Recently, a microbial community of the pancreas and the biliary tract cancers has been investigated to identify a distinct microbiota composition associated with cancer in the pancreatic and biliary habitats [11][12][13][14][15]. Moreover, some researchers are exploring how to change the pancreatic-biliary microbiota to slow tumor growth [16,17].…”

Advances in the Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Premalignant Pancreatic Lesions

“…Finally, there are promising new avenues for pancreatic cancer diagnostics, such as machine learning algorithms and quantitative assessments of microvesicle-derived DNA and RNA. In addition, recent research has provided fascinating insight into the role of the microbiome in PDAC development and progression, suggesting that characteristic alterations in the oral, gut, and intratumoral microbiota could be used to diagnose PDAC and even predict treatment outcomes [ 80 , 81 , 82 ]. Similarly, the ongoing development of biosensors based on technologies such as nanoribbons, microfluidics, elliptical dichroism spectrometry, and quantum dots could lead to powerful and high-throughput means of detecting relevant biomarkers to diagnose PDAC [ 83 , 84 , 85 , 86 ].…”

Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights

“…Another SCFA from the gastrointestinal (GI) microbiota, acetate, induces insulin secretion via the microbiome-brain β-cell axis controlling pancreatic bacterial overgrowth[ 92 , 93 ]. Tryptophan metabolism can serve as an immunomodulatory factor by overexpression of indoleamine2,3-dioxygenase1 which inhibits the maturation of CD11c and dendritic cells, and T-cell proliferation and by high expression of Kyn which leads to induction and activation of the aryl hydrocarbon receptor, leading to upregulation of programmed cell death protein 1 expression; enhancing the efficacy of antitumor adoptive T-cell therapy and reducing the rate of migration and invasion in both tumor-bearing mice and patients with PC[ 94 - 96 ].…”