# Bacterial Therapy of Cancer: A Way to the Dustbin of History or to the Medicine of the Future?
## 3 Tumor Microbiome: Peaceful Inhabitants or Malicious Instigators? Technological advances in DNA sequencing have provided unprecedented insights into the composition of the microbiomes, in particular of different parts of the human body, including malignant neoplasms [34]. Here, we should note that the study of the tumor microbiome is a quite difficult task. First of all, it should distinguish the tumors originating on mucosal surfaces that either harbor a diverse microbial community (microbiota) or are routinely exposed to microbes from the environment (i.e., naso- and orophynx, esophagus, gastrointestinal tract, or skin) from tumors in body sites that are typically considered sterile (the lung, liver, bladder, bone, blood, etc.). In the first case, it is necessary to detect a probably tiny difference in the composition of the tumor microbiome from that of the surrounding tissues, while in the second case, to be sure that there is no possible outside contamination introduced at the time of extraction or while manipulating a tumor tissue. This is of particular importance because the tumor microbiome was established to have a relatively low biomass. In the very recent and excellent work of [PERSON]. [PERSON] et al. [35; 36], which is the most rigorous and comprehensive survey of bacteria in human tumor samples to date [37; 38], the microbiome of 1526 samples from seven human tumor types (breast, lung, melanoma, pancreas, ovary, bone, and glioblastoma multiforme) was characterized. Authors used hundreds of negative controls and created a series of computational filters to remove the traces of any bacteria that could have come from outside the tumor samples. It was discovered that every single cancer type harbored metabolically active (live) bacteria, and that different cancer types harbor different bacteria species. The highest number and diversity of bacteria was revealed in breast cancers. Moreover, many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors. Electron microscopy visualization of these bacteria demonstrated that they prefer to locate in specific places inside the cancer cells--close to the cell nucleus. Possibly, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. Thus, the observations of many scientists who had been reporting the presence of certain microbes inside the tumor and tumor cells for more than a hundred years can be considered convincingly confirmed. However, where do microorganisms come from inside a \"sterile\" tumor? It can be assumed that, as tumors develop, their disorganized, leaky vasculature may allow circulating bacteria to enter, and the immunosuppressed environment as well as the presence of nutrients within the hypoxic region may provide a safe haven for them. Intratumor bacteria may also arise from the normal adjacent tissues if the latter are typically a place of their colonization. However, even if bacteria do live inside tumors and tumor cells, the main and most interesting question--whether these bacteria are directly involved in the process of oncogenesis--still remains unanswered. The authors emphasize that there is no evidence that the microbiome or any specific taxa _cause_ cancer, at least outside of other factors of carcinogenesis [35]. Therefore, in the next section, we will consider cases where the link between bacterial infection and tumor development are believed to be established. Tumorigenic Effect of Bacteria: Microbes, Which Are Typically Linked to Cancer, and Probable Mechanisms of Carcinogenic Action  
Before discussing the intriguing question of the role of bacteria in carcinogenesis, it is worth clarifying what it means to participate in carcinogenesis.