Shifts in the Fecal Microbiota Associated with Adenomatous Polyps.
Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas.



We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547).



Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism.



These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer.



This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85-94. ©2016 AACR.
Department of Surgery, Mayo Clinic, Rochester, Minnesota.|Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Vanessa L
VL
Hale
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Jun
J
Chen
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Stephen
S
Johnson
Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Sean C
SC
Harrington
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Tracy C
TC
Yab
Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
Thomas C
TC
Smyrk
Department of Surgery, Mayo Clinic, Rochester, Minnesota.
Heidi
H
Nelson
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Lisa A
LA
Boardman
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Brooke R
BR
Druliner
Division of Gastroenterology, Kaiser Permanente, Oakland, California.
Theodore R
TR
Levin
Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana.
Douglas K
DK
Rex
Denver Department of Veterans Affairs Medical Center, University of Colorado Denver School of Medicine, Denver, Colorado.
Dennis J
DJ
Ahnen
University of Arizona Cancer Center, Tucson, Arizona.
Peter
P
Lance
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. chia.nicholas@mayo.edu ahlquist.david@mayo.edu.
David A
DA
Ahlquist
Department of Surgery, Mayo Clinic, Rochester, Minnesota. chia.nicholas@mayo.edu ahlquist.david@mayo.edu.|Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.|Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Nicholas
N
Chia
D018256:Adenomatous Polyps / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000382:microbiology* / Q000473:pathology; D003113:Colonoscopy / Q000379:methods; D015179:Colorectal Neoplasms / Q000517:prevention & control; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology*; D011379:Prognosis; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D013048:Specimen Handling
D012336:RNA, Ribosomal, 16S
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