Microbial dysbiosis and epigenetics modulation in cancer development – A chemopreventive approach
Introduction
Earlier studies have shown that there is a direct association between the human body’s microbiome and several disorders, such as metabolic illnesses, intestinal complications, and communicable illnesses [[1], [2], [3]]. The projected masses of microorganisms that populate human beings determine a definite correlation with the host, but dysbiotic relations can lead to the promotion of inflammatory disorders and cancers. Microbiomes can either augment the development of cancer or may have anti-tumour effect [[4], [5], [6]]. The microbiota can encourage carcinogenesis in three ways. First, the genotoxins secreted can damage the host DNA. Secondly, the development of inflammation as a result of toxins and metabolites produced by microbiota [7,8]. Thirdly, the dysregulation of the immune system in reaction to different microbes may lead to the development of cancer [9]. The different microbiomes get involve in cancer onset at diverse locations within the body due to the difference in the physiological ecosystem at various locations of the human body. Compromised microbiota can accelerate tumourigeneses via different processes, as has been reported in earlier studies [7,8]. This review focuses on cancers promoted by pathogens at different sites such as colon, lung, ovarian and breast along with the genetic and epigenetic alterations/aberrations induced or aberrations corrected.
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Cancers triggered by specific microbes
A variety of viruses and bacteria harbour the gut and the oral cavity. The gastrointestinal tract (GIT) is populated with a variety of microbes (i.e., bacteria, virus, and fungus species), among which, viruses are reported to be more assertive. The local microenvironment and the food intake decide the composition of the gut virome. Both, the microbes and the host live in a dynamic equilibrium however, viruses may invigorate some grade of an immune response without triggering signs [10,11].
Gut microbiome and cancer
The microorganisms involved in cancer progression depend on the locations involved and the microenvironment of the site, so different sites will harbour different microbes [16]. Esophageal cancer is one among the fatal cancers and upon analyzing the microbes of the Barrett esophagus and normal biopsy samples discloses a substantial variance between the microbiome of normal esophagus that is subjugated by the genera Streptococcus and in contrast comparatively plenty of Gram-negative anaerobic
Colorectal cancer
In recent past, numerous studies have reported the influence of the gut microbiome in colorectal cancer (CRC) [24]. CRC incidence is now reported in young adults and it is the second most frequent reason for mortality worldwide. Thus, detailed information about the functions, which gut microbes perform in the development of colorectal cancer is required. Herein, we have reviewed the recent developments related to the influence of gut microbes on the genetics and epigenetics of colorectal cancer
Lung cancer
Lung cancer has been one of the leading causes of cancer-related death in both genders worldwide and is on a rising trend. Owing to the poor prognosis, more than 50 % of the patients identified with lung cancer die within a year of diagnosis, while the rate of survival is around 5 years for >18 %. Although, both non-small cell lung carcinoma (NSCLC) that covers 85 % of lung cancers and small cell lung carcinoma (SCLC) that covers 15 % are well characterized, still very little is known about the
Breast cancer
A disparity in breast cancer occurrence among females with known risk factors remains a fascinating question that needs attention. Accumulating pieces of evidence suggest that microbial dysbiosis predisposes the body for cancer initiation and progression, therefore, dysbiotic microbiota demonstrated a potential correlation with breast cancer progression. Herein, we have attempted to provide a comprehensive view on microbial composition in the breast tissue of healthy and in breast cancer (BC)
Ovarian cancer
Ovarian cancer is the second most deadly gynaecological cancer among all other cancers, and it is the 5th leading death-causing cancer in women. Numerous studies have indicated that our potential cancer risk may be exacerbated by the different pathogens such as viruses, bacteria, fungi, and parasites in our body. Earlier, it has been reported that differences in the individual's microbiome can be correlated with varying susceptibility towards this disease [158,159]. In addition to the
Impact of gut microbes on epigenome
Diet can impact epigenetic alterations accompanying illness and may change gene expression through epigenetic mechanisms [176,177]. The epigenetic mechanisms comprise methylation of DNA, post-translational modification of histone proteins as well as alterations in non-coding RNAs. The microbial action on diet can also produce certain complexes that change the epigenetic pathways including altering substrates used for methylation or synthesize the complexes that change the action of epigenetic
Influence of dietary polyphenols on microbiome and epigenetics
Dietary phenols undergo massive microbial alterations in the colon and these dietary polyphenolic compounds have been correlated with stimulating epigenetic mechanisms, however, many intermediate compounds yet persist to be studied [207]. Dietary chemopreventive compounds including Epigallocatechin-3-gallate (EGCG), Quercetin, and sulphoraphane have been shown to influence the progression of cancer [208]. EGCG is a polyphenol, generally present in Green tea that has been stated to influence
Conclusions and future prospects
The onco-microbiome is an emerging field of science and is catching the interest of researchers. Researchers are now focusing on finding the impact of gut microbiota on cancer therapies and the outputs of the studies are aiding in-depth understanding of cancer genesis. Metagenome in humans is much more diverse and complicated compared to their genome, where the microbes interact consistently with the host. This dynamic interaction affects different physiological processes, whereas dysbiosis may
Funding
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Declaration of Competing Interest
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