The Microbiome in PDAC—Vantage Point for Future Therapies?

Abstract

Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to understand and exploit this knowledge for the treatment of human malignancies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor with limited therapeutic options and a poor long-term survival. Recent data have revealed fascinating insights into the role of the tumoral microbiome in PDAC, with profound implications for survival and potentially therapeutic outcomes. In this review, we outline the current scientific knowledge about the clinical and translational role of the microbiome in PDAC. We describe the microbial compositions in healthy and tumoral pancreatic tissue and point out four major aspects of the microbiome in PDAC: pathogenesis, diagnosis, treatment, and prognosis. However, caution must be drawn to inherent pitfalls in analyzing the intratumoral microbiome. Among others, contamination with environmental microbes is one of the major challenges. To this end, we discuss different decontamination approaches that are crucial for clinicians and scientists alike to foster applicability and physiological relevance in this translational field. Without a definition of an exact and reproducible intratumoral microbial composition, the exploitation of the microbiome as a diagnostic or therapeutic tool remains theoretical.

Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery

“…Pathogenic flora that contribute to cancer can spread locally (e.g., from the vagina to the cervix ( 217 ), or from the respiratory system to the lungs ( 218 )) or distally as bacteria originating in the oral cavity (e .g., Porphyromonas gingivalis, Tannerella forsythia, Veillonella parvula, F. nucleatum, Parvimonas Micra , etc. ), have been found associated with cancers of the esophagus ( 219 ), GI/colon ( 220 ) pancreas ( 221 ) and liver ( 87 ). Once cancer is established, microorganisms can infiltrate the tumor microenvironment (TME), working synergistically with tumor-infiltrated leukocyte subpopulations (LSPs); tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), CD4+CD25+Foxp3+Tregs creating a robust and strong immunosuppressive barrier ( 37 , 87 , 222 , 223 ).…”

Pancreatic Ductal Adenocarcinoma and Nutrition: Exploring the Role of Diet and Gut Health

“…Multiple microbial species from fecal and oral samples have demonstrated potential as diagnostic markers for PDAC, showing associations with the CA 19-9 marker [45]. These include increased levels of Streptococcus and Veillonella and decreased levels of Faecalibacterium prausnitzii [46].…”

“…Additionally, PDAC patients exhibited lower levels of butyrate-producing bacteria. Given these variations in microbial composition between early and advanced cancer patients compared to healthy individuals, microbial dysbiosis holds promise as a potential diagnostic and prognostic marker for this disease [45].…”

Invasive Candidiasis in Patients with Solid Tumors: A Single-Center Retrospective Study

“… 9 In healthy individuals, candida and other microorganisms mainly play physiological functions and contribute to individual homeostasis, however, in patients with solid tumors, candida and other microorganisms play different roles and may play a role in promoting the progression of solid tumors. 10 And patients with solid tumors may develop neutropenia, further leading to poor prognosis. 11 According to previous research results, the most common invasive candida infection in patients with solid tumors is Candida albicans , followed by Candida parapsilosis, tropical Candida and Candida glabrata , but it is changing like non Candida albicans infection.…”