Date of Award
2025
Document Type
Open Access Thesis
Department
Biological Sciences
First Advisor
Maria Majorette Pena
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC in patients older than 50 years has been decreasing, however, CRC in patients less than 50 years known as early onset colorectal cancer (EOCRC) has steadily increased since the 1990’s and is expected to increase by 90% in colon cancer and 124% in rectal cancer by 2030. While EOCRC has been linked to typical risks associated with late onset CRC, its causes and mechanisms are still unknown.
I hypothesize that the increased risk of EOCRC may be associated with exposure to antibiotics (Abx) and the western diet. Antibiotics are indispensable in the treatment of infectious diseases. However, its overuse, particularly in infants and children, has increased globally with over one million doses prescribed unnecessarily each year. While Abx is effective against pathogenic bacteria, it also targets gut microbiota, which are important for proper development of the immune system and metabolic processes. The western diet is characterized by its high-fat and low fiber content. I hypothesize that exposure to Abx and the western diet alters the gut microbiota and increases the risk for EOCRC. This hypothesis was tested on mouse models of CRC. In previous experiments, our results indicate that multiple exposures to azithromycin increased tumor burden in the distal rectum of treated mice.
In this study, C57BL/6 male mice were given commonly prescribed pediatric Abx (azithromycin) via oral gavage at different developmental stages, then injected them with azoxymethane (AOM), a carcinogen, to induce tumor development. Control mice were treated with polyethylene glycol. The mice were either fed a lowfat diet or a high-fat diet (representative of the western diet). Fecal pellets were collected during the duration of the experiment to analyze the gut microbiome changes.
The mice were sacrificed at the end of the experiment to observe tumor development, the abx and high-fat diet treated mice had the highest tumor burden. DNA sequencing of the fecal pellets revealed that dysbiosis occurred and was gut microbiome changes were more prominent in abx and high-fat diet treated mice. These results indicate that abx and high-fat diet cause dysbiosis which increases the risk of EOCRC.
Rights
© 2025, Varsha Gowda
Recommended Citation
Gowda, V.(2025). The Impact of Pediatric Antibiotics and the Western Diet on the Risk of Early Onset Colorectal Cancer. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/8583