Relationship between obesity-related colorectal tumors and the intestinal microbiome: an animal-based trial

J Cancer Res Clin Oncol. 2023 Jul;149(8):5265-5277. doi: 10.1007/s00432-022-04477-1. Epub 2022 Nov 18.

Abstract

Purpose: Obesity is a risk factor for colorectal cancer (CRC), and the intestinal microbiome is considered to contribute to CRC and obesity. Nonetheless, the role of the intestinal microbiome in obesity-related CRC is unclear. This study aimed to clarify the relationship between obesity-related CRC and the intestinal microbiome using a mouse model.

Methods: We compared an obese and insulin-resistant type 2 diabetes mouse model [KKAy] to wild-type mice (WT) [C57BL/6 J]. Azoxymethane was intraperitoneally injected to develop a mouse model CRC. At 26 weeks, we compared the number of tumors and the intestinal microbiome. We also compared them across two models, namely, antibiotic cocktail and co-housing.

Results: In all models, KKAy mice had a significantly greater number of tumors than WT mice. Analysis showed that the distribution of the intestinal microbiome changed in both models; however, no difference in tumor development was observed. Tumor expression was suppressed only in the antibiotic cocktail model of WT, whereas KKAy mice bore tumors (C57Bl/6 J: KKAy, 0/9:8/8; p < 0.001). KKAy mice remained predominantly tumor-bearing in all treatments.

Conclusion: Based on the results, the intestinal microbiome may not be associated with tumorigenesis in obesity-related CRC. It may be necessary to think of other facts linked to obesity-related CRC.

Keywords: Colorectal cancer; Intestinal microbiome; Mouse model; Obesity; Principal component analysis; Tumorigenesis.

MeSH terms

  • Animals
  • Colorectal Neoplasms* / pathology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / pathology
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / complications