Bartlett, Ashley; Phatak, Sumira; Hintze, Korry; Benninghoff, Abby (Utah State University)
Faculty Advisor: Benninghoff, Abby (College of Agriculture and Applied Sciences; Animal, Dairy, and Veterinary Sciences Department)
The gut microbiome modulates various physiological functions related to cancer development including inflammation, cell proliferation, apoptosis, and angiogenesis. Patients with inflammatory bowel disease have a microbiome distinct from healthy controls with consistent observations of reduced gut biomass, decreased diversity within the community, and altered relative abundance. Although a consensus cancer-related microbiome has not been identified, several pathogenic species play an instrumental role in the progression of colitis and tumorigenesis, including: Streptococcus bovis, Helicobacter pylori, Enterococcus faecalis, Clostridium septicum, and Escherichia coli. Gut microbial composition is highly responsive to diet and inadequate intake of micronutrients is a critical feature of the Western dietary pattern. Gut dysbiosis has been proposed to further limit mineral uptake and impair vitamin synthesis, predisposing the host to micronutrient deficiency. Dietary bioactives, such as those in green tea, may function as a mediator between the gut microbiome and basal diet to ultimately prevent colitis associated colorectal cancer (CAC). The overarching objective of our work is to determine the impact of ancestral or multi-generational consumption of the total Western diet (TWD) in a murine model of CAC. Our previous work is the first to investigate how diet induced transgenerational inheritance affects CAC outcome. Our data suggested that multigenerational patterns of exposure to the TWD altered both phenotype and gene expression in third generation offspring. Supplementation with green tea appeared to be most promising after consumption of TWD for multiple generations. Considering that gut microbes are inherited maternally after colonization during vaginal birth, the gut microbiome is a missing piece in this disease model puzzle. The hypothesis of our current project is to investigate whether intake of TWD influences the transmission of microbes and whether CAC outcome is reflected by altered gut microbial composition. Based on other work, we expect the healthy control to possess an abundance of varied bacterial taxa that maintain protective epithelial barrier function and overall homeostasis. On the other hand, a high fat diet would promote increased intestinal permeability, a substantial shift at the phyla level, and increased production of pro-inflammatory cytokines. After TWD consumption, we expect an overall negative phenotypic outcome within the gut microbiome, that includes a breakdown of the epithelial barrier and introduction of pathogenic bacteria. These harmful bacteria tend to thrive on simple sugars that are common in the Western dietary pattern and tend to produce metabolites known as endotoxins that promote dysbiosis.