Elsevier

Seminars in Cancer Biology

Volume 86, Part 3, November 2022, Pages 666-681
Seminars in Cancer Biology

Microbial dysbiosis and epigenetics modulation in cancer development – A chemopreventive approach

https://doi.org/10.1016/j.semcancer.2021.06.024Get rights and content

Abstract

An overwhelming number of research articles have reported a strong relationship of the microbiome with cancer. Microbes have been observed more commonly in the body fluids like urine, stool, mucus of people with cancer compared to the healthy controls. The microbiota is responsible for both progression and suppression activities of various diseases. Thus, to maintain healthy human physiology, host and microbiota relationship should be in a balanced state. Any disturbance in this equilibrium, referred as microbiome dysbiosis becomes a prime cause for the human body to become more prone to immunodeficiency and cancer. It is well established that some of these microbes are the causative agents, whereas others may encourage the formation of tumours, but very little is known about how these microbial communications causing change at gene and epigenome level and trigger as well as encourage the tumour growth. Various studies have reported that microbes in the gut influence DNA methylation, DNA repair and DNA damage. The genes and pathways that are altered by gut microbes are also associated with cancer advancement, predominantly those implicated in cell growth and cell signalling pathways. This study exhaustively reviews the current research advancements in understanding of dysbiosis linked with colon, lung, ovarian, breast cancers and insights into the potential molecular targets of the microbiome promoting carcinogenesis, the epigenetic alterations of various potential targets by altered microbiota, as well as the role of various chemopreventive agents for timely prevention and customized treatment against various types of cancers.

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.

Section snippets

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

None.

Declaration of Competing Interest

None.

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