title: The gut microbiota in conventional and serrated precursors of colorectal cancer.
abstract: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types.
  
  
  
  Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases.
  
  
  
  Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Brandilyn A
authors.initials: BA
authors.lastname: Peters
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Dominianni
authors.affiliation: Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Shapiro
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Church
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, NY, USA.|Department of Cell Biology, New York University School of Medicine, New York, NY, USA.|NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Miller
authors.affiliation: Kips Bay Endoscopy Center, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yuen
authors.affiliation: Kips Bay Endoscopy Center, New York, NY, USA.
authors.forename: Hal
authors.initials: H
authors.lastname: Freiman
authors.affiliation: Kips Bay Endoscopy Center, New York, NY, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Lustbader
authors.affiliation: Kips Bay Endoscopy Center, New York, NY, USA.
authors.forename: James
authors.initials: J
authors.lastname: Salik
authors.affiliation: Kips Bay Endoscopy Center, New York, NY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Friedlander
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.|NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA. Jiyoung.Ahn@nyumc.org.|NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA. Jiyoung.Ahn@nyumc.org.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
mesh_terms: D000236:Adenoma / Q000382:microbiology*; D000368:Aged; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D001483:Base Sequence; D003111:Colonic Polyps / Q000382:microbiology*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000382:microbiology*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial
keywords: Adenoma; Cancer; Colorectal; Microbiome; Microbiota; Polyp; Serrated