Microbial and metabolic profiles unveil mutualistic microbe-microbe interaction in obesity-related colorectal cancer

• Published in: Cell reports. Medicine Vol. 5; no. 3; p. 101429
• Main Authors: Li, Jinming, Chen, Ziying, Wang, Qinying, Du, Lutao, Yang, Yongzhi, Guo, Fanying, Li, Xinxiang, Chao, Yanjie, Ma, Yanlei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.03.2024; Elsevier
• Subjects: colorectal cancer; Colorectal Neoplasms - microbiology; cross-feeding; gut microbiota; Humans; lipid metabolism; Metabolome; metagenome; Microbial Interactions; Microbiota; obesity; Obesity - metabolism; short-chain fatty acid; short-chain fatty acid; colorectal cancer; metagenome; cross-feeding; lipid metabolism; obesity; gut microbiota; metabolome
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2024.101429

Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening. [Display omitted] •Obese colorectal cancer (CRC) manifests distinct microbial features•Altered fatty acids and phospholipids are associated with obese CRC•Cross-feeding between probiotics and tumor-enriched species may drive obese CRC•Microbial biomarkers demonstrate promise for BMI-stratified CRC screening Li et al. unveil microbial and metabolic features in colorectal cancer (CRC) associated with obesity and discover potential cross-feeding interactions between probiotics and tumor-promoting species, shedding light on the mechanisms behind elevated CRC risk in the obese population.