Role of microbiome in cancer progression

The human microbiome is one of the most diverse and well-characterized microbiomes, consisting of many bacteria, protozoa, fungi, and viruses. It coexists with the host in a dynamic symbiosis as a meta-organism. These microorganisms inhabit different anatomical parts of the host, with the oral cavity, gut, and skin being the most prominently inhabited. With the advent of Next-generation sequencing (NGS), 16S rRNA sequencing, whole genome sequencing, and omics technologies such as transcriptomics, lipidomics, metagenomics, and meta proteomics, it has become possible to characterize different microbial niches in the human body like lungs, kidney, and stomach which were uncharacterized before (Zhang et al., 2019, Aggarwal et al., 2023). Over time, the microbiome has co-evolved with its human host, performing a remarkable role in maintaining human health. The disturbance in this equilibrium paves the way for different pathological conditions.

In a more scientific term “microbiome” refers to the total genetic material of all microorganisms living in the human body; it is frequently thought of as the body’s secondary genome. The additional set of genes belonging to the microbiome plays a part in regulating host physiological functions via different metabolites produced by bacterial metabolism (Aggarwal et al., 2023). Microbes usually flourish in an environment that offers favorable conditions to support their growth and, therefore, have access to altering the different environmental conditions of the host, including their ambient temperature, pH, oxygen, and nutrient uptake (Aggarwal et al., 2023).

The factors that determine the population and composition of the human microbiota can be categorized broadly into extrinsic and intrinsic factors and are depicted in Fig. 1. Extrinsic factors include lifestyle factors like diet, medication use, stress levels, and hygiene practices that can influence the human microbiota (Avuthu and Guda, 2022, Garrett, 2015, Candela et al., 2014). In contrast, intrinsic factors are the internal elements within the body that impact the composition and balance of microorganisms living within various niches. Intrinsic factors include genetic predispositions, immune system function, hormonal levels, and metabolic processes. Intrinsic factors can also be influenced by extrinsic factors. Changes in the natural environment of the body, whether due to extrinsic, extrinsic or pathological factors, can prompt a shift in microbial composition and its function termed as dysbiosis.

Dysbiosis often involves changes in the relative abundance of different microbial species, including an overgrowth of potentially pathogenic bacteria and a reduction in beneficial microbes. Certain microbial species associated with dysbiosis can produce molecules such as lipopolysaccharides (LPS) or flagellin or that can activate inflammatory pathways in the host (Potrykus et al., 2021). Dysbiosis can also lead to reactive oxidative stress (ROS) mediated cell death as the production of ROS is enhanced during inflammatory responses causing DNA damage. The relationship between the microbiome and cancer is a complex and evolving area of research. Chronic inflammation is known to significantly increase the risk of cancer by creating an environment that promotes tumor growth through enhanced cell proliferation, angiogenesis, and genomic instability (Singh et al., 2019). Some microbes in the microbiome like H. pylori can directly induce gastric cancer by releasing its virulent proteins in gut epithelia (Wroblewski et al., 2010).

The primary challenge in cancer treatment arises from the fact that many cancers go unnoticed and show no symptoms during their early stages. By the time they are detected in their advanced stages, they often become life-threatening. Microbial composition and their metabolic signatures can be employed as biomarkers for the early detection of cancer (Zwezerijnen-Jiwa et al., 2023). Further, microbiomes and their associated products can be used for immunotherapy as microbiomes influences immune responses.

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