Research Proposal:Prebiotics as modulators of the intestinal microbiome: An innovative and natural strategy for the treatment of cancer Ref. No. SSTCRC088
1. Introduction
The intestinal microbiome is characterized by a complex population of microorganisms with diverse structures and genome, whose variety of strains result in different and specific stimuli in the gastrointestinal tract. Studies report that these microorganisms, when stimulated by prebiotics (functional ingredients) and through the production of metabolites, induce cell differentiation and inhibit the growth and development of the hyperproliferative epithelium. Cancer is a significant public health problem, the second leading cause of death worldwide. The effectiveness of the treatment becomes limited due to the process of drug resistance. It is estimated that resistance to chemotherapy is the cause of treatment failure in 90% of patients with metastatic cancer. In addition, its treatment generates a strong economic impact, with an annual global cost of US$ 160 billion. In addition, the currently available drugs are toxic to normal cells, thus affecting the patient's quality of life. Considering that prebiotics can act in the modulation of the intestinal microbiome, inhibiting the proliferation and stimulating the death of neoplastic cells, this work search to evaluate in vitro and in silico the anticancer potential of the metabolites resulting from prebiotic fermentation by the microorganisms that make up the intestinal microbiome, providing new clues for the treatment of neoplasms. The metabolites will be produced through the mixed culture of probiotics in a medium containing prebiotics. Then, they will be identified and purified by High Performance Liquid Chromatography (HPLC). To evaluate their anticancer potential, the following assays will be performed: cell viability, clonogenicity, cell cycle, death, invasion, and migration.
2. Objectives
The supernatant containing the metabolites resulting from the fermentation of prebiotics in co-culture inhibited the viability and proliferation of the colorectal cancer line (HT-29). Furthermore, they were able to induce cell cycle entrainment in the G0-G1 phase and to inhibit the migration of neoplastic cells after 48h of treatment. However, the analysis of cell death profile indicated that treatment with the supernatant containing metabolites induced low percentage of cell death in the HT-29 cell line after 48h of incubation. Therefore, it is concluded that the tests were able to confirm the cytotoxic effect, antiproliferative and antimigratory supernatant containing metabolites produced by probiotics from prebiotic fermentation, proving that this approach can be promising for the treatment of colorectal cancer.
3. Cooperation required
People who are expertise in cell cycle, death, protein expression and in silico analysis.
4. Expected Benefits&Outcomes
This project aims to contribute to the development of new molecules for the treatment of neoplasms, the consolidation of research in Pernambuco (Brazil) and the training of human resources. It is also expected to yield 10 academic papers.