Altered Tissue Metabolites Correlate with Microbial Dysbiosis in Colorectal Adenomas

Abstract

Several studies have linked bacterial dysbiosis with elevated risk of colorectal adenomas and cancer. However, the functional implications of gut dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the “metabolome”, which may contribute to the development of neoplasia in the large bowel. We assessed the metabolome in normal rectal mucosal biopsies of 15 subjects with colorectal adenomas and 15 nonadenoma controls by liquid chromatography and gas chromatography time-of-flight mass spectrometry. Quantitative real-time PCR was used to measure abundances of specific bacterial taxa. We identified a total of 274 metabolites. Discriminant analysis suggested a separation of metabolomic profiles between adenoma cases and nonadenoma controls. Twenty-three metabolites contributed to the separation, notably an increase in adenoma cases of the inflammatory metabolite prostaglandin E2 and a decrease in antioxidant-related metabolites 5-oxoproline and diketogulonic acid. Pathway analysis suggested that differential metabolites were significantly related to cancer, inflammatory response, carbohydrate metabolism, and GI disease pathways. Abundances of six bacterial taxa assayed were increased in cases. The 23 differential metabolites demonstrated correlations with bacteria that were different between cases and controls. These findings suggest that metabolic products of bacteria may be responsible for the development of colorectal adenomas and CRC.

Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer

“…Secreted bioactive metabolites represent another way in which microbial populations interact with the host and has likely relevance to CRC 88, 89, 98–100 . Two classes of microbial metabolites with particular relevance to tryptophan metabolism and CRC are short chain fatty acids and indole compounds 101 .…”

Gut Microbiome and Colorectal Adenomas

“…Findings from a recent study suggests that there is a correlation between bacterial dysbiosis, the metabolome, and colorectal adenomas [79]. More studies are needed to fully explore the relationship between the microbiota, metabolome, adenomas, and CRC.…”

The human microbiome: opportunities and challenges for clinical care

“…Commonly precipitated by external factors such as exposure to antibiotics, dysbiosis can lead to normally benign microbial communities becoming pro‐inflammatory, invasive or being overgrown by pathogens . In the GIT, for example, dysbiosis has been implicated in a range of disorders, including inflammatory bowel disease, metabolic disorders and oncogenesis …”

“…56 In the GIT, for example, dysbiosis has been implicated in a range of disorders, including inflammatory bowel disease, 54 metabolic disorders 57 and oncogenesis. 58 Disease resulting from the disruption of commensal populations is not limited to the GIT. Bacterial vaginosis (BV), the most common vaginal disorder in women of reproductive age, 59 is believed to occur not as the result of any single aetiological agent, but as the result of a shift in the composition of vaginal microbiota.…”