Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Sep 29, 2018; 9(2): 47-58
Published online Sep 29, 2018. doi: 10.4291/wjgp.v9.i2.47
Gut microbiome profiling and colorectal cancer in African Americans and Caucasian Americans
Lulu Farhana, Fadi Antaki, Farhan Murshed, Hamidah Mahmud, Stephanie L Judd, Pratima Nangia-Makker, Edi Levi, Yingjie Yu, Adhip PN Majumdar
Lulu Farhana, Farhan Murshed, Hamidah Mahmud, Pratima Nangia-Makker, Yingjie Yu, Adhip PN Majumdar, Department of Internal Medicine, John D Dingell Veterans Affairs Medical Center, Detroit, MI 48201, United States
Lulu Farhana, Fadi Antaki, Pratima Nangia-Makker, Yingjie Yu, Adhip PN Majumdar, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, United States
Fadi Antaki, Stephanie L Judd, Division of Gastroenterology, John D Dingell VA Medical Center, Detroit, MI 48201, United States
Pratima Nangia-Makker, Adhip PN Majumdar, Department of Medicine, Karmanos Cancer Institute, Detroit, MI 48201, United States
Edi Levi, Department of Pathology Service, John D Dingell VA Medical Center, Detroit, MI 48201, United States
Author contributions: Farhana L contributed to study design, performed the experiments, data analysis and interpretation and wrote the manuscript; Antaki F and Judd SL performed the colonoscopy; Murshed F performed experiments and reviewed the manuscript; Mahmud H laboratory supported and reviewed the manuscript; Nangia-Makker P, Levi E and Yu Y laboratories provided material support; Majumdar APN was the principal investigator who conceptualized the study, revised and approved the final version of the manuscript.
Supported by Department of Veteran Affairs, No. 1I101BX001927; National Institutes of Health, No. 1R21CA175916.
Institutional review board statement: The study followed a Full Board Review by the Wayne State University Institutional Review Board.
Informed consent statement: All routine colonoscopy, collection of colonic effluents and biopsy specimens from the patients were performed after obtaining informed consent and ethical permission.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
ARRIVE guidelines statement: The ARRIVE Guidelines had been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Adhip PN Majumdar, DSc, PhD, Professor, Department of Internal Medicine, John D Dingell Veterans Affairs Medical Center, 4646 John R, Detroit, MI 48201, United States. a.majumdar@wayne.edu
Telephone: +1-313-5764460 Fax: +1-313-5761112
Received: May 11, 2018
Peer-review started: May 11, 2018
First decision: July 10, 2018
Revised: August 8, 2018
Accepted: August 26, 2018
Article in press: August 26, 2018
Published online: September 29, 2018
Processing time: 140 Days and 8.5 Hours
Abstract
AIM

To determine whether and to what extent the gut microbiome is involved in regulating racial disparity in colorectal cancer (CRC).

METHODS

All patients were recruited and experiments were performed in accordance with the relevant guidelines and regulations by the Institutional Review Boards (IRB), committees of the John D. Dingell VAMC and Wayne State University guidelines. African American (AA) and Caucasian American (CA) patients were scheduled for an outpatient screening for colonoscopy, and no active malignancy volunteer patients were doubly consented, initially by the gastroenterologist and later by the study coordinator, for participation in the study. The gut microbial communities in colonic effluents from AAs and CAs were examined using 16sRNA profiling, and bacterial identifications were validated by performing SYBR-based Real Time PCR. For metagenomic analysis to characterize the microbial communities, multiple software/tools were used, including Metastats and R statistical software.

RESULTS

It is generally accepted that the incidence and mortality of CRC is higher in AAs than in CAs. However, the reason for this disparity is not well understood. We hypothesize that the gut microbiome plays a role in regulating this disparity. Indeed, we found significant differences in species richness and diversity between AAs and CAs. Bacteroidetes was more abundant in AAs than in CAs. In particular, the pro-inflammatory bacteria Fusobacterium nucleatum and Enterobacter species were significantly higher in AAs, whereas probiotic Akkermansia muciniphila and Bifidobacterium were higher in CAs. The polyphyletic Clostridia class showed a divergent pattern, with Clostridium XI elevated in AAs, and Clostridium IV, known for its beneficial function, higher in CAs. Lastly, the AA group had decreased microbial diversity overall in comparison to the CA group. In summary, there were significant differences in pro-inflammatory bacteria and microbial diversity between AA and CA, which may help explain the CRC disparity between groups.

CONCLUSION

Our current investigation, for the first time, demonstrates microbial dysbiosis between AAs and CAs, which could contribute to the racial disparity of CRC.

Keywords: Human gut; Microbiome; Colorectal cancer; Fusobacterium nucleatum; African Americans; 16S RNA profiling; Metagenomics

Core tip: Several studies have demonstrated that the incidence of colorectal cancer (CRC) is higher in African Americans than Caucasian Americans. Reasons for this racial disparity are unknown. The current study, for the first time, demonstrated that dysbiosis in the gut microbiome plays a determinant role in the racial disparity of CRC. Determining the influence of the microbiota on the risk of developing CRC will have a major impact on health, since early-stage CRC hinges on the ability to detect early pathological changes. Subsequent translational studies could also be developed to alter microbiota with medications or diet, thus reducing the risk of developing CRC.