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Impact of sugary drinks on gut microbiota and development of young-onset colorectal cancer

Award Number: R21CA258134
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Impact of sugary drinks on gut microbiota and development of young-onset colorectal cancer - Project Summary One of the most disturbing phenomena in colorectal cancer (CRC) in the US in the past four decades is its increasing incidence and mortality in adults younger than 50 years old. Over the same time period, the consumption of sugar-sweetened beverages (SSBs) has dramatically increased. Notably, more than 60% of adolescents and young adults in the US consume at least one can (12 fl. oz.) of SSBs on a given day, suggesting a potential link between SSBs and young-onset CRC. However, it is unclear if there are direct, causal links and what the underlying molecular mechanisms would be. Our laboratory recently showed a direct, causal link between SSBs and CRC using adenomatous polyposis coli (Apc)-mutant mice, which are a model for early- stage colon adenoma (precancerous polyps). Apc-mutant mice treated with high-fructose corn syrup (HFCS, the main sweetener of SSBs) via oral gavage for 6–8 weeks showed an increase in the total tumor number, size, and grade, independent of obesity. Our preclinical studies suggest that consuming SSBs may shorten the time in which benign polyps develop into CRC in humans, explaining why young-onset CRC is currently on the rise. However, it remains unclear how HFCS does this. Diet plays a dominant role in shaping the gut microbiome, and an unhealthy diet can lead to dysbiosis, an imbalance in gut microbiota. A link has been shown between dysbiosis and CRC development. However, studies on the causal and mechanistic interrelationships among diet, gut microbiota, and CRC are still lacking. We previously observed that liquid HFCS dramatically increases the concentration of fructose (>5 mM) in the colonic lumen in mice, which may cause dysbiosis in the colon. Furthermore, our preliminary metagenomics and metabolomics data from wild-type mice have shown that chronic HFCS treatment increases the abundance of specific microbes and metabolic pathways that are implicated in human CRC development. Based on these data, we hypothesize that HFCS may facilitate CRC tumorigenesis and show the characteristics of young-onset CRC such as mucinous and signet ring features in tumors by altering the composition and function of gut microbiota. To test our hypothesis, we will use humanized Apc-mutant mice—in which a human microbiome has been established through fecal microbiota transplantation—and ex vivo 3D intestinal and tumor organoids. By completing the proposed project, we will be able to (1) determine the mechanistic and causal relationships between sugar-induced microbiota and young-onset CRC tumorigenesis; and (2) identify sugar-specific microbes or metabolites that can potentially be used as biomarkers and/or therapeutic targets in young-onset CRC patients. In sum, the proposed study will significantly impact our understanding of the etiology of young- onset CRC development and progression, potentially improving the prevention and clinical management of the disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2021	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	000	2	11/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2021	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	000	2	3/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	000	2	5/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = -$1 )
2023	2021	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	000	1	4/20/2023	NEW	-$160,000
2023	2021	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	002	1	5/24/2023	NEW	-$120,263
2023	2021	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	001	2	4/20/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$159,999
2023	2021	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	003	2	5/24/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$120,263
														Subtotal = -$1

Issue Date FY: 2021 ( Subtotal = $411,400 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Cause and Prevention Research	000	1	4/15/2021	NEW	$411,400
														Subtotal = $411,400

Grand Total All Awards = $411,399

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Impact of sugary drinks on gut microbiota and development of young-onset colorectal cancer

Award Number: R21CA258134

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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