Abstract
Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic promoters, or indirectly, through interactions with the human gut microbiota. The preponderant evidence derived from information reported over the last 10 years confirms that antibiotic exposure tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics, and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed. The information is in the end considered from the perspective of the most recent findings on the tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems to stages characterized for a lack of coordination among their components of prokaryotic origin, which is promoted by injuries caused by environmental insults.
Highlights
Introduction of Immune Checkpoint Inhibitors25 BC–50 ACXVIII Century AC to Present ca. 1940 ca. 1970 recentlyA third point of convergence between bacteria and cancer relates to the role, mentioned above, of the human microbiota as a global homeostasis regulator by which it provides protection against a number of diseases, including cancer
Antibiotics are the kind of compounds that have the potential of modifying cancer risk due to their ability to act as extrinsic environmental chemical carcinogenic factors and to alter the normal balance of the microbiota towards a more pro-carcinogenic composition
Data from this study showed that cancer incidence increased with the number of prescriptions, and that the extent of the association of the relative risk with antibiotic exposure varied with tumor type, being greatest in tumors of endocrine glands, followed in decreasing order by cancers of the prostate, breast, lung, colon and ovary [131]
Summary
In the continuous process through which living creatures kept progressively attaining levels of increasing structural and functional complexity, bacteria appeared much earlier than humans on the earth’s biosphere. The gut microbiota is known to establish a gut-organ network [26] that supports interactions with non-colonic microbiota [27] and with central homeostatic-regulatory controls, such as the immune system [28,29,30], the endocrine system [31], metabolism [32,33], the intrinsic circadian clock [34], brain function [35], and others Through this network, the gut microbiota influences the onset, severity and outcome of diseases that cause high levels of morbidity and mortality among humans, including cardiovascular [36,37], liver [38], autoimmune [39] or infectious diseases [40], as well as cancer [41]. It has become clear that the progression of human civilization to more sedentary ways of life (e.g., the transition from hunter-gatherer communities to societies with agriculturalist and pastoralist economies) followed by the creation of ever larger cities and the establishment of better ways of communication between cities allowed the appearance of sustained infections by human-adapted bacterial pathogens [56,57], many of which were of zoonotic origin, transmitted from animals in various ways [58,59,60]
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