Role of the microbiome in non-gastrointestinal cancers

Abstract

"The forgotten organ", the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as "local" and "systemic", "cancer-stimulating" and "cancer-suppressing" effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment.

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle

“…As such, it has the foremost metabolic effect of all microbiomes. As the most frequently investigated organ system, the gastrointestinal tract has been used as a model for understanding the host-microbiota and disease relationship (Pevsner-Fischer et al, 2016;Schwabe & Jobin, 2013). Other organs, such as the skin, oral cavity and female genital tract, that also contain a considerable number of microorganisms have been less frequently studied (Schwabe & Jobin, 2013).…”

“…Furthermore, an estimated 93 283 people are expected to die of this disease. Pancreatic cancer is an aggressive malignancy, with a low rate of survival and therapeutic success (Mitsuhashi et al, 2015;Pevsner-Fischer et al, 2016). Therefore, it is important to further understand its pathogenesis and to search for new diagnostic and therapeutic alternatives (Mitsuhashi et al, 2015;Zambirinis et al, 2014).…”

“…Lung cancer is an important cause of mortality worldwide. Although about 90 % of cases are attributed to smoking, only 10-15 % of smokers develop cancer, suggesting other influences, such as chronic lung inflammation (Houghton, 2013;Pevsner-Fischer et al, 2016).…”

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…(214). Earlier work demonstrated that the host (e.g., gut) microbiome dynamically interacts, i.e., influences and is affected by, inflammation including pro-tumor inflammatory pathways, and that microbial dysbiosis is implicated in many tumors, notably lung carcinomas (218,219). Of note, preclinical studies have identified gut bacteria that influence tumor immunity and response to immunotherapy and chemotherapy, in addition to other seminal reports whose findings accentuate the role of the host microbiome in tumor biology, as discussed below (220)(221)(222).…”

Microbiota as a mediator of cancer progression and therapy

“…20-22 In addition, microbial dysbiosis has also been observed in other forms of cancers including breast, lung, urogenital, and liver, which was the subject of a recent review. 23 …”