Association between upper digestive tract microbiota and cancer-predisposing states in the esophagus and stomach.
BACKGROUND
The human upper digestive tract microbial community (microbiota) is not well characterized and few studies have explored how it relates to human health. We examined the relationship between upper digestive tract microbiota and two cancer-predisposing states, serum pepsinogen I/pepsinogen II ratio (PGI/II; predictor of gastric cancer risk) and esophageal squamous dysplasia (ESD; the precursor lesion of esophageal squamous cell carcinoma; ESCC) in a cross-sectional design.


METHODS
The Human Oral Microbe Identification Microarray was used to test for the presence of 272 bacterial species in 333 upper digestive tract samples from a Chinese cancer screening cohort. Serum PGI and PGII were determined by ELISA. ESD was determined by chromoendoscopy with biopsy.


RESULTS
Lower microbial richness (number of bacterial genera per sample) was significantly associated with lower PGI/II ratio (P = 0.034) and the presence of ESD (P = 0.018). We conducted principal component (PC) analysis on a β-diversity matrix (pairwise difference in microbiota), and observed significant correlations between PC1, PC3, and PGI/II (P = 0.004 and 0.009, respectively), and between PC1 and ESD (P = 0.003).


CONCLUSIONS
Lower microbial richness in upper digestive tract was independently associated with both cancer-predisposing states in the esophagus and stomach (presence of ESD and lower PGI/II).


CONCLUSIONS
These novel findings suggest that the upper digestive tract microbiota may play a role in the etiology of chronic atrophic gastritis and ESD, and therefore in the development of gastric and esophageal cancers.
Authors' Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville; National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland; Forsyth Institute, Cambridge; Wellesley College, Wellesley; Harvard School of Dental Medicine, Boston, Massachusetts; and Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Guoqin
G
Yu
Mitchell H
MH
Gail
Jianxin
J
Shi
Vanja
V
Klepac-Ceraj
Bruce J
BJ
Paster
Bruce A
BA
Dye
Guo-Qing
GQ
Wang
Wen-Qiang
WQ
Wei
Jin-Hu
JH
Fan
You-Lin
YL
Qiao
Sanford M
SM
Dawsey
Neal D
ND
Freedman
Christian C
CC
Abnet
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D003430:Cross-Sectional Studies; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D009367:Neoplasm Staging; D020116:Pepsinogen A / Q000097:blood; D020115:Pepsinogen C / Q000097:blood; D011230:Precancerous Conditions / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology
D014408:Biomarkers, Tumor; D020115:Pepsinogen C; D020116:Pepsinogen A