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

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.
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openaccess
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dissertation
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http://creativecommons.org/licenses/by/4.0/