Impact of Probiotics on Metabolic Interactions for the Prevention of Colorectal Cancer: A Comprehensive Network with Molecular Docking Studies

Abstract

Colorectal cancer (CRC) ranks as the third most diagnosed cancer globally and stands as the second leading cause of cancer-related deaths. Research suggests that modifications in the gut microbiome may influence the onset and advancement of cancer. Furthermore, the dietary habits of an individual and the quantity of alcohol intake can influence the microbiome, thereby affecting the progression of colorectal cancer. A diet emphasizing fiber consumption is regarded as advantageous, as it includes short-chain fatty acids like butyrate, which exhibit antitumor characteristics. Moreover, contemporary treatment approaches, including chemotherapy, are associated with a range of side effects. This study employed a network pharmacology-based approach to identify potent metabolites of gut microbiota and its key target. Active metabolites generated by gut microbiota from fermented foods (Ogi, Iru, Fufu, and Garri) were obtained utilizing the gutMGene database, and targets related to these metabolites were identified through the Swiss Target Prediction tool. The targets related to CRC were sourced from the GeneCards database. Molecular docking tests were conducted to validate the findings and evaluate the binding affinity of the metabolites with the target protein. The research identified the crystal structure of human anaplastic lymphoma kinase (ALK) as a potential therapeutic target for colorectal cancer. The metabolites (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid, uridine-5'-diphosphate, adenosine triphosphate, and lomerizine demonstrated significant binding affinity with the target proteins, yielding docking scores of -8.0, -7.4, -7.6, and -7.9 kcal/mol, respectively. In comparison, the FDA-approved drugs fluorouracil and capecitabine exhibited docking scores of -4.6 and -6.7 kcal/mol. This study employs a network pharmacology approach to identify significant metabolites of gut microbiota and key targets for the treatment of colorectal cancer (CRC). The results were corroborated through molecular docking experiments, establishing a basis for subsequent research on anti-colorectal cancer metabolites and their mechanisms of action.