Metabolite profile comparisons between ascending and descending colon tissue in healthy adults

Abstract

BACKGROUND Obesity is a risk factor for colorectal cancer, yet metabolic distinctions between healthy right and left colon tissue, before cancer is diagnosed, remains largely unknown. This study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight, overweight, and obese adults. AIM To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer risk. METHODS Global, non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite profiles. The colon tissue and stool metabolome of healthy adults (n = 24) was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal cancer. RESULTS Ascending and descending colon contained 504 host, food, and microbiota-derived metabolites from normal weight, overweight and obese adults grouped according to body mass index. Amino acids, lipids, and nucleotides were among the chemical types that further differentiated from the stool metabolite profiles. Normal weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations, whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults (P < 0.05). Obese adults had trimethylamine N-oxide, endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending colon. Primary and secondary bile acids, vitamins, and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese adults. CONCLUSION There were metabolite profile differences between right-ascending and left-descending colon tissue in healthy adults. Colon lipids and other metabolites in obese and overweight adults were distinguished from normal weight participants and associated with gut inflammation, nutrient absorption, and products of microbiota metabolism.