Research Projects

Rationale of the research: Fermented food derived microbes characterized as probiotics are shown to exhibit diverse health benefits. Recent times these fermented foods, considered as functional food contains probiotics which provide oncometabolites and tumor-suppressive metabolites upon metabolic transformations of dietary components in the gut. Dysbiosis of gut microbiota is associated with development of colorectal cancer. Hence, providing beneficial microbes to gut through these fermented food sources is considered to be one of the preventives and interventional therapy for colon cancer. PI’s lab has been working on valuable microbial strains isolated from fermented foods. One of the fermented brine mango pickle isolate Bacillus licheniformis PUFST35 was characterized for probiotic effects, stability and safety. Preliminary experiments with crude cell free extract showed cytotoxicity towards colon cancer cell line HT-29. However, further purification and characterization of the active principle from the crude extract and its mechanism of anti-colon cancer activity remains to be determined. Objectives: 1) To elucidate the mechanism of action of active principle/s of extract by in vitro cell culture model. 2) To evaluate the anti-colon cancer activity in an in vivo animal model. 3) To Purify and characterize active principle/s. Methodology: Crude extract to be tested for anti-proliferation action using various colorectal carcinoma cell line as culture model. Mechanistic study to elucidate anti-cancer action by apoptosis assay and cell cycle analysis, migration assay, anti-inflammatory biochemical assay and macrophage secretion measured by ELISA and global transcriptomic analysis. Findings from cell culture study will be emulated in mice model of colon cancer to understand anti-cancer action in in vivo model by histopathology, biochemical, metabolomic and microbiome analysis. Purifying the crude extract to obtain active principle and characterization by cytotoxicity assay and safety evaluation towards human blood will be carried out. Bioavailability of active principle in cellular fraction will be determined. Significance of study: Anti-cancer properties of the strain Bacillus licheniformis PUFST35 will be confirmed. Principle component responsible for anti-cancer activity will be elucidated. Safety and efficacy of the strain as well as the extract will be assessed by in vivo studies. In vivo animal studies for anti-colon cancer will provide pre-clinical data for further validation of the probiotic strain as well as the active principle. The proposed project will also generate new information on the compounds of probiotic origin including onco-metabolites and products of their interaction with other gut metabolites in both the management of colon cancer in particular and in gut homeostasis in general. On in-depth characterization of the strain and the active principle will pave way for novel functional probiotic based treatment of colon cancer.