INFLUENCES OF HIGH-FAT DIET AND ANTRODIA CAMPHORATA IN EARLY LIFE ON INTESTINAL TUMORIGENSIS LATER IN LIFE

Lin, Ting-Chun

Publication:
INFLUENCES OF HIGH-FAT DIET AND ANTRODIA CAMPHORATA IN EARLY LIFE ON INTESTINAL TUMORIGENSIS LATER IN LIFE

dc.contributor.advisor	Zhenhua Liu
dc.contributor.author	Lin, Ting-Chun
dc.contributor.department	University of Massachusetts Amherst
dc.date	2024-03-27T18:28:46.000
dc.date.accessioned	2024-04-26T16:04:07Z
dc.date.available	2024-04-26T16:04:07Z
dc.date.submitted	September
dc.date.submitted	2023
dc.description.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.
dc.description.degree	Doctor of Public Health (DrPH)
dc.description.department	Public Health
dc.identifier.doi	https://doi.org/10.7275/35600434
dc.identifier.orcid	https://orcid.org/0000-0001-6212-017X
dc.identifier.uri	https://hdl.handle.net/20.500.14394/19407
dc.relation.url	https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=3966&context=dissertations_2&unstamped=1
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.source.status	published
dc.subject	Early-onset colorectal cancer
dc.subject	early-life nutrition
dc.subject	mushroom supplementation
dc.subject	childhood obesity
dc.subject	probiotics
dc.subject	Molecular, Genetic, and Biochemical Nutrition
dc.title	INFLUENCES OF HIGH-FAT DIET AND ANTRODIA CAMPHORATA IN EARLY LIFE ON INTESTINAL TUMORIGENSIS LATER IN LIFE
dc.type	openaccess
dc.type	article
dc.type	dissertation
digcom.contributor.author	isAuthorOfPublication\|email:tony82605@gmail.com\|institution:University of Massachusetts Amherst\|Lin, Ting-Chun
digcom.identifier	dissertations_2/3013
digcom.identifier.contextkey	35600434
digcom.identifier.submissionpath	dissertations_2/3013
dspace.entity.type	Publication