Gut microbiome development along the colorectal adenoma-carcinoma sequence

Background and Aims: Colorectal cancer (CRC), a commonly diagnosed cancer in the elderly often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however have not been surveyed in a comprehensive manner. Here we perform the first metagenomic-wide association study (MGWAS) on stools from healthy controls, advanced adenoma and carcinoma patients, and reveal the possible impact of various risk factors, especially red meat versus fruit and vegetable consumption on gut microbial alterations along the adenoma-carcinoma sequence.

Patients and Methods: Data from 147 Caucasians undergoing colonoscopy according to national screening recommendations for CRC as well patients with suspected CRC undergoing colonoscopy as part of the clinical workup were included in the final analysis. Fresh stool samples were collected from all patients and subjects. Metagenomic sequencing for comparison of the fecal microbiome in healthy controls, advanced adenoma and carcinoma patients was performed. A detailed medical history, including life style and dietary questionnaires, was obtained.

Results: Carcinoma-enriched bacteria that produce short chain fatty acids, the major energy source for colonocytes, through amino acid fermentation and/or bacteria that metabolize bile acids, for example, B. massiliensis, B. dorei, B. vulgates, Parabacteroides merdae, A. finegoldii and B. wadsworthia, showed a positive correlation with consumption of red meat and/or a negative correlation with consumption of fruits and vegetables, suggesting a common pathway in colorectal tumourigenesis.

Conclusion: The results imply that high intake of red meat relative to fruits and vegetables is associated with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest fecal microbiome-based strategies for early diagnosis and treatment of colorectal adenoma or carcinoma.