Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study.
BACKGROUND
Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low.


METHODS
Microbiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT +) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods.


RESULTS
Of 95 FIT + participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations.


CONCLUSIONS
If confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
James J
JJ
Goedert
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Yangming
Y
Gong
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
Xing
X
Hua
BGI, Shenzhen, China.
Huanzi
H
Zhong
BGI, Shenzhen, China.
Yimin
Y
He
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Peng
P
Peng
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
Guoqin
G
Yu
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Wenjing
W
Wang
Institute of Genome Sciences, University of Maryland Medical School, Baltimore MD, USA.
Jacques
J
Ravel
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
Jianxin
J
Shi
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Ying
Y
Zheng
D000236:Adenoma / Q000175:diagnosis / Q000382:microbiology*; D000368:Aged; D001483:Base Sequence; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000382:microbiology*; D055088:Early Detection of Cancer / Q000379:methods; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012372:ROC Curve; D017422:Sequence Analysis, DNA
D012336:RNA, Ribosomal, 16S
Cancer screening; China; Colorectal adenoma; Colorectal cancer; Feces; Microbiota