The Gut Microbiome in Environmentally-Induced Oncogenesis: From Sentimental Biomarkers to Precision Therapeutics- A Comprehensive Review

Abstract

The gut microbiome serves a primary interface between host physiology and harmful environmental xenobiotics like microplastics, heavy metal and pesticides. The persistent exposure to these pollutants is the primary cause of profound dysbiosis, characterized by a sharp reduction in commensal bacteria, such as lactobacillus species along with the proliferation of proinflammatory cytokines. This typical microbial imbalance translocates endotoxins to trigger the activation of TLR4 and NLRP3 inflammasome pathways by compromising the integrity of barrier. This results in the initiation of chronic inflammation and along with chronic stress inside the gut, in order to activate the sequence known as inflammation induced carcinoma. Advancements in metabolomics and metagenomics have highlighted several metabolic and microbial signatures, like alteration of tryptophan and short chain fatty acids, that serve as a signature for the exposure of these pollutants. To assess the long-term risk of carcinogenesis, the integration of machine learning algorithms with these datasets will surely enable the researchers to develop exposure scores. Furthermore, a great deal of advancements has been observed in the development of therapeutic strategies, and they have evolved from the traditional restoration of microbiota by giving prebiotics, FMT and probiotics to other high precision interventions like synthetic biology, phage therapy and CRISP-Cas9, offering a more efficient surgical and programmable engineering of gut associated commensal microbiota to neutralize oncogenes at the site of dysplasia. Despite the potential of techniques like non-invasive biomarkers identification and precision-based therapeutics, there is a dire need to overcome methodological standardization along with successful clinical translation of complex and integrated muti-omics data across the globe. This review highlights how the concepts of personalized health interventions can be practiced if the environment and health related gaps are fulfilled, eventually transforming the toxic nature of microbes into a programmable shield that actively regulates the immune components and protects environmentally induced oncogenes.