*EMBARGOED All research presented at the ACG Annual Scientific Meeting is strictly embargoed until Monday, October 17, 2016 at 8:00 am EDT.
Poster 111 Colorectal Cancer and Racial Disparity: Gut Microbiome as a Potential Regulator
Author Insight from Lulu Farhana, PhD (John D. Dingell VA Medical Center, Wayne State University), Fadi Antaki, MD, Stephanie Judd, MD, Pratima Nangia-Makker, PhD, Sachin Goyal, MD, Timothy Hadden, PhD, Yingjie Yu, PhD, Edi Levi, MD, and Adhip Majumdar, PhD
What’s new here and important for clinicians?
While the difference in incidence and mortality of colorectal cancer (CRC) among African-Americans (AAs) and Caucasian Americans (CAs) is well documented, little is known about the underlying factors that are responsible for these differences. Various independent factors like diet and socioeconomic status have been proposed. In our study, we propose a unifying model with differences in gut microbiome as the central theme.
Farhana L et al. examined the colonic effluent (washings collected during colonoscopy) from patients aged 40-80 undergoing outpatient colonoscopy and analyzed the microbiota, and secondary bile acid specifically, Deoxycholic Acid (DCA), Lithocolic Acid (LCA). In addition, expression of several stem cell markers was also examined. We found a significantly higher number of pro-inflammatory bacteria like Enterobacteria in AAs, compared to CAs. In contrast, anti-inflammatory bacteria like Bifidobacteria and Lactobacillus were less abundant in AAs. Increase in pro-inflammatory bacteria in AAs was associated with marked rise in the levels of the secondary bile acids LCA and DCA, which are the products of microbial biotransformation, present primarily in the human large intestine. Interestingly, DCA and LCA induced the generation of cancer stem cells in the colonic mucosa (evidenced by increased colonosphere formation), accompanied by increased expression of long non-coding RNAs (lncRNA), CCAT2 (Colon Cancer Associated Transcript 2) and/or HOTAIR (Hox anti-sense intergenic RNA).
These observations for the first time demonstrate a pivotal role of gut microbiome in regulating disparity in CRC between the AAs and CAs in the United States. This study was supported by grants to Dr. Majumdar from the National Institutes of Health/National Cancer Institute and the U.S. Department of Veterans Affairs.
What do patients need to know?
Bacteria present in the human gut play an important role in the maintenance of normal gastrointestinal functionality. This is marked by a delicate balance between the disease-forming (pathogenic) and friendly (commensal) bacteria. Lifestyle factors like diet and weight can disturb this balance, resulting in overgrowth of pathogenic bacteria. This can lead to increases in certain diseases like inflammatory bowel disease and also CRC, which is the second leading cause of cancer-related deaths in the United States. However, the incidence and mortality of colon cancer is different among various racial groups and African Americans (AAs) share the largest burden of CRC in the United States. Interestingly, in our lab we have found a higher number of harmful bacteria and a lower number of “friendly” bacteria in the colon of AAs as compared to CAs. These changes were accompanied by an increase in certain markers of cancer initiation process. The reasons for changes in bacterial populations between AAs and CAs are not fully known. However, increasing evidence suggests that dietary components like vegetables, fiber and vitamin D are associated with a lower risk of colon cancer, whereas red meat and a diet rich in saturated animal fat with an increased risk of colon cancer. Our observations further solidify the important role played by a “healthy” diet in our fight against cancer.
Sachin Goyal, MD
Adhip Majumdar, PhD
Lulu Farhana, PhD
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