Bacteriostatic mode of action of plant sesquiterpenes on the human microbial pathogen Helicobacter pylori and microbial communities of the gut

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Sesquiterpenes are a structurally diverse family of plant natural products, prevalent among the solanaceous plants that are common in the diet such as tomatoes, potatoes, and peppers. While these compounds play critical roles in mediating ecological interactions between plants, insects and microbes, they also provide a rich source of high-value bioactives for human uses ranging from antibiotics, anticancer and anti-inflammatory agents, to flavours and fragrances. Though we ingest sesquiterpenes from dietary sources, little is known about how these compounds affect human microbes and microbial communities and the chemical ecology of the human gut. This gap in our knowledge will be addressed in the ISP. Initially, we will focus on a detailed mode of action study of capsidiol, an isoprenoid from peppers, and its bacteriostatic effect on the gut microbe Helicobacter pylori. These investigations will expand to consider the effects of capsidiol and related isoprenoid compounds on the gut microbial communities more broadly. To date, we have successfully isolated capsidiol from peppers, established several strains of H. pylori in the lab and conducted growth curve measurements. Additionally, we have evaluated the growth inhibitory activities of alpha-copaene from potatoes. The establishment of this experimental system and the successful pilot studies set the stage for metabolomics and transcriptomics studies to elucidate the manner in which isoprenoids in the diet perturb microbial metabolic function and gene expression. Subsequent studies will compare the action of a range of dietary (constitutive) sesquiterpenes, including alpha-copaene from potato varieties in collaboration with SCRI. Following targeted studies with H. pylori, we seek to study the effect of individual and mixtures of dietary phytochemicals on communities of commensal gut microorgansms, through close interactions with the IFR Gut ISP.

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