Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2020; 26(3): 335-352
Published online Jan 21, 2020. doi: 10.3748/wjg.v26.i3.335
Metabolite profile comparisons between ascending and descending colon tissue in healthy adults
Bridget A Baxter, Kristopher D Parker, Michael J Nosler, Sangeeta Rao, Rebecca Craig, Catherine Seiler, Elizabeth P Ryan
Bridget A Baxter, Kristopher D Parker, Elizabeth P Ryan, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Fort Collins, CO 80523, United States
Michael J Nosler, University of Colorado Health Gastroenterology Clinic, Fort Collins, CO 80524, United States
Sangeeta Rao, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, United States
Rebecca Craig, Harmony Surgery Center, Fort Collins, CO 80528, United States
Catherine Seiler, Director of Clinical Operations, Harmony Surgery Center, Fort Collins, CO 80523, United States
Author contributions: Ryan EP and Nosler MJ designed research and maintained study oversight; Nosler MJ, Craig R and Seiler C conducted human tissue sample collections; Baxter BA and Parker KD analyzed the metabolite profile and microbiome data collected from stool and colon; Parker KD and Rao S performed statistical analysis; Baxter BA, Parker KD, and Ryan EP wrote the manuscript; Ryan EP had primary responsibility and all authors approved the final product.
Supported by the CancerCure Foundation and the University of Colorado Cancer Center Support Grant, Division of Cancer Control and Prevention (Aurora, CO), No. P30CA046934.
Institutional review board statement: Colorado State University Institutional Review Board No. 15-6051, and University Colorado Health-North Institutional Review Board No. 0010144.
Informed consent statement: Participants provided written informed consent.
Conflict-of-interest statement: Authors have nothing to disclose.
Data sharing statement: Metataxonomics sequence data are available via NCBI SRA BioProject Accession PRJNA594611 and on this project’s GitHub repository github.com/kdprkr/ConjurersBrew.
STROBE statement: The authors have read the STROBE guidelines, and the manuscript was prepared and revised according to the STROBE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Elizabeth P Ryan, PhD, Associate Professor, Department of Environmental and Radiological Health Sciences, Colorado State University, 1617 Campus Delivery, Fort Collins, CO 80523, United States. e.p.ryan@colostate.edu
Received: October 22, 2019
Peer-review started: October 15, 2019
First decision: November 13, 2019
Revised: December 11, 2019
Accepted: December 21, 2019
Article in press: December 21, 2019
Published online: January 21, 2020
Processing time: 85 Days and 15.2 Hours
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.

Keywords: Colon; Ascending; Descending; Metabolomics; Obesity; Stool

Core tip: This study identified metabolite profile differences between right-ascending and left-descending colon from normal, overweight or obese adults. We also show that stool metabolite composition does not accurately reflect the right-ascending colon. There is limited knowledge of human colon small molecules and metabolite signatures that may impact colon cancer risk. Colon cancer of the right-ascending colon has a poorer prognosis and reduced survival outcome when compared to colon cancer on the left-descending colon. Diet and lifestyle are additional factors of overweight and obesity that may influence colon tissue metabolite composition with respect to inflammation. Right and left colon metabolite profiles may be helpful to evaluate after interventions that seek to prevent or mitigate cancer risk.