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  3. Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development

  • Adv Sci (Weinh). 2023 Jul 3;e2206238. doi: 10.1002/advs.202206238.
Ling Wang 1 2 3,  Yi-Xuan Tu 1 2,  Lu Chen 1 2,  Yuan Zhang 1 2,  Xue-Ling Pan 1 2,  Shu-Qiao Yang 1 2,  Shuai-Jie Zhang 1 2,  Sheng-Hui Li 1 2,  Ke-Chun Yu 1 2,  Shuo Song 1 2,  Hong-Li Xu 4,  Zhu-Cheng Yin 4,  Jun-Qiu Yue 4,  Qian-Lin Ni 5,  Tang Tang 5,  Jiu-Liang Zhang 6,  Min Guo 2,  Shuai Zhang 1 3,  Fan Yao 1 2 3,  Xin-Jun Liang 4,  Zhen-Xia Chen 1 2 3 7 8
Affiliations

Affiliations

  • 1 Hubei Hongshan Laboratory, Wuhan, 430070, China.
  • 2 Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, 430070, China.
  • 3 Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518000, China.
  • 4 Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, China.
  • 5 Wuhan Metwell Biotechnology Co., Ltd. Wuhan, Wuhan, 430075, China.
  • 6 College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
  • 7 Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, 518000, China.
  • 8 College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, 430070, China.
PMID: 37400423 DOI: 10.1002/advs.202206238
Abstract

Men demonstrate higher incidence and mortality rates of colorectal Cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both APCMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

Keywords

colorectal cancer; fecal microbiota transplantation; gut microbiome; sexual dimorphism.

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