Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients

Abstract

Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers

“…Furthermore, alterations of gut microbiota modulate tryptophan levels, the precursor of serotonin, a critical neuroendocrine cell effector responsible for the carcinoid syndrome associated with functional tumors [74]. Microbiota can also influence chemotherapy response, which may represent a pathway to increase the efficiency of checkpoint inhibitors [68,75].…”

Molecular Biomarkers in Cancer

“…Stool samples are also useful for microbiota profiling, which has also gained relevance as a biomarker, not only for CRC but also for other gastrointestinal cancers, including pancreatic cancer [ 96 , 97 ]. Moreover, the bacterial profile can also predict response to cancer therapy.…”

Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target

“…Patients with PDAC had an increased phylum Proteobacteria (such as Gammaproteobacteria) and a decreased phylum Firmicutes (such as butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia intestinalis) when compared with healthy controls (139). Additionally, several recent review articles have underscored the importance of the gut microbiome in the development and progression of PDAC (140)(141)(142).…”