Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer

Abstract This study investigated the sex-specific correlation between obesity and colorectal cancer emphasizing a more pronounced association in males. Estrogen, chromosomal genes, and gut bacteria were assessed in C57BL6/J male, female and ovariectomized (OVX) female mice, subjected to either a low...

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Main Authors: Yoo-Mee Chang, Yoo-Ree Kang, Yu-Gyeong Lee, Mi-Kyung Sung
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-53861-z
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author Yoo-Mee Chang
Yoo-Ree Kang
Yu-Gyeong Lee
Mi-Kyung Sung
author_facet Yoo-Mee Chang
Yoo-Ree Kang
Yu-Gyeong Lee
Mi-Kyung Sung
author_sort Yoo-Mee Chang
collection DOAJ
description Abstract This study investigated the sex-specific correlation between obesity and colorectal cancer emphasizing a more pronounced association in males. Estrogen, chromosomal genes, and gut bacteria were assessed in C57BL6/J male, female and ovariectomized (OVX) female mice, subjected to either a low-fat diet (LFD) or high-fat diet (HFD) for 14 weeks. Induction of colon tumor involved azoxymethane (10 mg/kg) administration, followed by three cycles of dextran sulfate sodium. Male mice on HFD exhibited higher final body weight and increased colon tumors compared to females. Colonic mucin 2 expression was significantly higher in females. HFD-modulated differentially expressed genes numbered 290 for males, 64 for females, and 137 for OVX females. Only one up-regulated gene (Gfra3) overlapped between females and OVX females, while two down-regulated genes (Thrsp and Gbp11) overlapped between males and OVX females. Genes up-regulated by HFD in males were linked to cytokine-cytokine interaction, HIF-1 signaling pathway, central carbon metabolism in cancer. Sex-specific changes in gut microbial composition in response to HFD were observed. These findings suggest a male-specific vulnerability to HFD-induced colon tumor formation, implicating key genes and colonic bacteria in colon tumorigenesis.
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spelling doaj.art-261423c7e5094515a8bcf79ce6fc56992024-03-05T19:02:13ZengNature PortfolioScientific Reports2045-23222024-02-0114111410.1038/s41598-024-53861-zSex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancerYoo-Mee Chang0Yoo-Ree Kang1Yu-Gyeong Lee2Mi-Kyung Sung3Department of Food and Nutrition, College of Human Ecology, Sookmyung Women’s UniversityDepartment of Food and Nutrition, College of Human Ecology, Sookmyung Women’s UniversityDepartment of Food and Nutrition, College of Human Ecology, Sookmyung Women’s UniversityDepartment of Food and Nutrition, College of Human Ecology, Sookmyung Women’s UniversityAbstract This study investigated the sex-specific correlation between obesity and colorectal cancer emphasizing a more pronounced association in males. Estrogen, chromosomal genes, and gut bacteria were assessed in C57BL6/J male, female and ovariectomized (OVX) female mice, subjected to either a low-fat diet (LFD) or high-fat diet (HFD) for 14 weeks. Induction of colon tumor involved azoxymethane (10 mg/kg) administration, followed by three cycles of dextran sulfate sodium. Male mice on HFD exhibited higher final body weight and increased colon tumors compared to females. Colonic mucin 2 expression was significantly higher in females. HFD-modulated differentially expressed genes numbered 290 for males, 64 for females, and 137 for OVX females. Only one up-regulated gene (Gfra3) overlapped between females and OVX females, while two down-regulated genes (Thrsp and Gbp11) overlapped between males and OVX females. Genes up-regulated by HFD in males were linked to cytokine-cytokine interaction, HIF-1 signaling pathway, central carbon metabolism in cancer. Sex-specific changes in gut microbial composition in response to HFD were observed. These findings suggest a male-specific vulnerability to HFD-induced colon tumor formation, implicating key genes and colonic bacteria in colon tumorigenesis.https://doi.org/10.1038/s41598-024-53861-z
spellingShingle Yoo-Mee Chang
Yoo-Ree Kang
Yu-Gyeong Lee
Mi-Kyung Sung
Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
Scientific Reports
title Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
title_full Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
title_fullStr Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
title_full_unstemmed Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
title_short Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer
title_sort sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity associated colorectal cancer
url https://doi.org/10.1038/s41598-024-53861-z
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