Date of Award
2025
Document Type
Open Access Dissertation
Department
Biological Sciences
First Advisor
Maria Marjorette Pena
Abstract
Colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer-related deaths in the United States, primarily affecting individuals over 55 years of age. While CRC incidence in older adults has declined in recent decades, the incidence in younger individuals under 55, known as early onset colorectal cancer (EOCRC), has risen sharply. Projections indicate a 90 to 124 percent increase in EOCRC among Americans aged 20 to 34, and a 28 to 46 percent increase among those aged 35 to 49. Most EOCRC cases are sporadic, without family history or known genetic predisposition, and the causes behind this trend remain unclear. One hypothesis is that early life exposure to environmental factors, or exposomes, may increase EOCRC risk. Among these, antibiotics are particularly concerning due to their widespread use in early childhood, their alignment with EOCRC birth cohorts, and their known impact on gut microbiota.
We hypothesized that early life antibiotic exposure induces gut dysbiosis and chronic inflammation, increasing susceptibility to colon tumor development. Using the A/J AOM (azoxymethane) mouse model, we tested whether repeated exposure to commonly prescribed antibiotics, including Amoxicillin and Azithromycin, would affect tumor development. Azithromycin treated mice showed significantly higher tumor burden in the distal colon compared to controls. 16S rDNA sequencing confirmed long term gut dysbiosis. ELISA and immunofluorescence revealed elevated inflammatory cytokines (IL1β, IL10) in plasma and increased colonic infiltration of immune cells (CD45 positive, F4/80 positive, and regulatory T cells).
To identify age specific vulnerability, mice were treated with Amoxicillin for seven days during either the perinatal period (5 days old) or early adulthood (4 weeks old). Only mice treated in the perinatal period showed a significant increase in tumor burden. Microbiome analysis identified bacterial families potentially linked to EOCRC risk.
In conclusion, our findings suggest that early life antibiotic exposure may promote EOCRC by inducing persistent gut dysbiosis and inflammation, highlighting a possible modifiable risk factor for this growing public health concern.
Rights
© 2025, Niti Ashvinkumar Jani
Recommended Citation
Jani, N. A.(2025). Effects of Commonly Prescribed Antibiotics on the Risk of Early Onset Colorectal Cancer. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/8581