Host-microbiota interactions and oncogenesis: Crosstalk and its implications in etiology
Introduction
The recent past has witnessed several breakthroughs in the field of microbiota mediated oncogenesis. The linkages of several microbes with cancer have appeared in recent past despite initial reluctance to accept this association. Around 20% of cancers are estimated to be associated with infections, making it a big portion for this public health problem [1]. Several mechanisms are credited for microbe-associated cancers and microbiota is an important component during the transformation of normal cell to the cancerous ones.The term microbiota is generally referred to microbial communities coexisting with an individual, and which influence several aspects of an individual's physiology. The ecosystem developed by these microbial communities within/on an individual regulates a number of biological processes, such as immune homeostasis, production of metabolites, digestion of complex food materials and protection against several pathogenic organisms etc. [2] (Fig. 1). Microbiota mediates the production of several mediators for protection from infections in addition to the production of several vitamins and important nutrients and their utilization from food nutrients [3]. Microbiota composition decides the fate of several diseases and therefore several studies have analyzed the normal and disease associated microbiota and the same is also applicable to carcinogenesis and cancer associated microbiota [4]. The transformation of normal microbiota to disease-associated microbiota is known as microbiota dysbiosis and its correction to normal microbiota through probiotics is suggested as an important approach for management of several diseases including cancer [5].
Though, several mechanisms are suggested for understanding the role of microbiota in cancer etiology, the most widely studied mechanism involves inflammatory regulation which was given considerable scientific attention due to its major involvement in microbiota and microbes associated carcinogenesis [6]. For instance, most studied Helicobacter pylori infection associated gastric cancer is also attributed to chronic inflammation and long term tissue injury, and this sequence is influenced by several other factors, including the composition of gut microbiota [7].
Nevertheless, the involvement of microbiota in oncogenesis involves several other mechanistic aspects that are relatively less discussed due to their specific involvement in certain types of cancers only, or the unavailability of sufficient data about their contribution. For instance, hormonal regulation is associated with certain kinds of cancer and recent studies have found that regulation of hormones is also affected by microbiota constituents and certain hormones play an important role in cancer development. This article tries to gather information about such microbiota associated oncogenesis mechanisms in order to generate more scope of discussion among scientific community.
Section snippets
Microbiota and oncogenesis: a multidimensional association
The mechanism through which microbial entities induce or promote cancers is generally considered to be systemic inflammation. The origin of this inflammation lies in dysbiosis. With the support from advanced sequencing technologies, we now know that microbiota gets deviated from its steady state in most of the diseases like metabolic syndromes to various cancer types like laryngeal, esophageal, breast, gastric, colon, pancreatic, and gallbladder carcinomas across the body. The generic evidence
Other important mechanisms for microbiota mediated cancer
There are several other mechanisms for microbiota mediated cancer that are sometimes specific to certain types of cancer. Certain cancers are associated with hormonal regulation. For instance, breast, ovary, endometrium, testis, prostate, thyroid and osteosarcoma are associated with hormones and share specific mechanisms of carcinogenesis, in which the exogenous and endogenous hormones lead to cell proliferation [29]. This model of cell proliferation is quite distinct from chemical
Hormone, microbiota and cancer triad
It has been understood that hormones can play an important role in the etiology of several cancer.The most important hormone associated cancer among males involve the prostate while among females, endometrium, breast, and ovary cancer are related to hormones, where hormones regulate the rate of cell division and influence the development of cancer under the influence of several other factors [36]. Studies have found a complex effect of hormone therapy during randomized trials on cancer risk
Bacterial effectors, cyclomodulins and cancer
Several bacteria are known to produce certain effector molecules with the ability to hijack host cell growth machinery [74]. These regulatory molecules exert a variety of effects on host cells. Some bacterial proteins themselves act as transcription factors. For example, transcription activator-like (TAL) effectors identified in certain plant bacteria, such as Xanthomonas oryzae, regulate transcription of important genes in host cells [75], though the identification of same regulators in human
Horizontal gene transfer and cancer
It is known that cell-free DNA can induce cell transformation and tumorigenesis under in vitro and in vivo conditions [85]. Even the cancer cells are known to release malignancy promoting factors in surrounding area prior to developing tumor associated vasculature system after cell death and consequent horizontal gene transfer (HGT) [86]. HGT is known as lateral genetic material exchange between organisms, instead of vertical gene transfer which occurs between generations and it is a common
Conclusion
There is significant evidence regarding mechanistic implications of microbes in the carcinogenic process, but the precise mechanisms underlying these associations are still lacking and studies investigating the mechanistic associations between infection and cancer are still ongoing. Most of such studies pertain to the involvement of inflammation in microbiota mediated cancer, while other studies are suggestive of the role of bacterial metabolites in carcinogenesis. Recently, the role of other
CRediT authorship contribution statement
Abdul Arif Khan: Writing – original draft, Supervision, Formal analysis, Data curation, Conceptualization. Vijay Nema: Writing – review & editing, Data curation. Mohd. TashfeenAshraf: Writing – review & editing, Investigation, Data curation.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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