title: Structural shifts of gut microbiota as surrogate endpoints for monitoring host health changes induced by carcinogen exposure.
abstract: This study monitored structural shifts of gut microbiota of rats developing precancerous mucosal lesions induced by carcinogen 1,2-dimethyl hydrazine (DMH) treatment using PCR-denaturing gradient gel electrophoresis (DGGE) and 454 pyrosequencing on the 16S rRNA gene V3 region. Partial least square discriminant analysis of DGGE fingerprints showed that the gut microbiota structure of treated animals was similar to that of the controls 1 and 3 weeks after DMH treatments, but significantly different 7 weeks after DMH treatments, when a large number of aberrant crypt foci (ACF) developed in their colons. Martens' uncertainty test, followed by anova test (P<0.05) identified Ruminococcus-like and Allobaculum-like bacteria as key variables for discrimination of DMH-treated rats from controls. Real-time PCR confirmed the significant increase of the Ruminococcus obeum and the Allobaculum-like bacteria in DMH-treated rats. UniFrac analysis based on V3 pyrosequencing further validated that the gut microbiota structures of treated and control animals were similar at an early stage, but segregated after ACF formation. Thirteen operational taxonomic units including Ruminococcus-like and Allobaculum-like bacteria were identified as key variables for the discrimination of DMH-treated rats from controls. Dynamic analysis of gut microbiota may become a noninvasive strategy for monitoring host health changes induced by carcinogen exposure.
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Menghui
authors.initials: M
authors.lastname: Zhang
authors.forename: Weiying
authors.initials: W
authors.lastname: Hua
authors.forename: Chenhong
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pang
authors.forename: Minjun
authors.initials: M
authors.lastname: Chen
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Mingmei
authors.initials: M
authors.lastname: Zhou
authors.forename: Shengli
authors.initials: S
authors.lastname: Yang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Dazheng
authors.initials: D
authors.lastname: Wu
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000009:adverse effects; D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D015415:Biomarkers; D002273:Carcinogens / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005798:Genes, Bacterial; D008297:Male; D054892:Metagenome; D010802:Phylogeny; D011230:Precancerous Conditions / Q000139:chemically induced / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D045857:Ruminococcus / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; D002273:Carcinogens; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D019813:1,2-Dimethylhydrazine