Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Author ORCID Identifier

https://orcid.org/0000-0001-6212-017X

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Public Health (DrPH)

Degree Program

Public Health

Year Degree Awarded

2023

Month Degree Awarded

September

First Advisor

Zhenhua Liu

Subject Categories

Molecular, Genetic, and Biochemical Nutrition

Abstract

Young-onset colorectal cancer (CRC) is a growing public health concern globally due to the increasing prevalence of westernized lifestyles during childhood and adolescence. Meanwhile, there have been reports of health-promoting effects, such as anti-inflammatory and anti-cancer properties, associated with Antrodia camphorata (AC), a unique fungus native to Taiwan. This study aimed to investigate the impact of early-life high-fat diet (HF) and AC supplementation on intestinal tumorigenesis in young adulthood, using APC1638N mice. Additionally, the study aimed to determine the role of Turicibacter, a probiotic negatively associated with diet-induced obesity, in colorectal tumorigenesis, and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. APC1638N mice were fed experimental diets from 4 to 12 weeks of age, equivalent to human childhood/adolescence, before switching to a normal maintenance chow diet for an additional 12 weeks up to 24 weeks of age, equivalent to young to middle adulthood in humans. Results showed that early-life HF increased body weight, fasting blood glucose levels, and intestinal tumor incidence and size, with elevated intestinal insulin-like growth factor 1 (IGF-1) receptor signaling. Additionally, early-life HF altered the microbiome composition, increasing the abundance of obesity-associated bacteria and decreasing the abundance of short-chain fatty acid (SCFA)-producing bacteria. In contrast, AC supplementation suppressed tumor incidence in females, reduced IGF-1 receptor signaling and Wnt/β-catenin signaling, suppressed intestinal inflammation, and increased the abundance of lean-associated, anti-inflammatory, and SCFA-producing bacteria. Furthermore, AC supplementation showed anti-CRC properties, which were further enhanced by the fermentation of Turicibacter, inhibiting tumorigenic serotonin and Wnt/β-catenin signaling and promoting reactive oxygen species (ROS)-mediated apoptosis in Caco-2 cells. These findings suggest that early-life dietary interventions may be effective in preventing or reducing CRC incidence in young adults, and that AC supplementation and probiotics fermentation may be potential complementary and alternative therapies.

DOI

https://doi.org/10.7275/35600434

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Download

Share

COinS