title: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations.
abstract: OBJECTIVE
  Investigation of microbe-metabolite relationships in the gut is needed to understand and potentially reduce colorectal cancer (CRC) risk.
  
  
  METHODS
  Microbiota and metabolomics profiling were performed on lyophilized feces from 42 CRC cases and 89 matched controls. Multivariable logistic regression was used to identify statistically independent associations with CRC. First principal coordinate-component pair (PCo1-PC1) and false discovery rate (0.05)-corrected P-values were calculated for 116,000 Pearson correlations between 530 metabolites and 220 microbes in a sex*case/control meta-analysis.
  
  
  RESULTS
  Overall microbe-metabolite PCo1-PC1 was more strongly correlated in cases than in controls (Rho 0.606 vs 0.201, P = 0.01). CRC was independently associated with lower levels of Clostridia, Lachnospiraceae, p-aminobenzoate and conjugated linoleate, and with higher levels of Fusobacterium, Porphyromonas, p-hydroxy-benzaldehyde, and palmitoyl-sphingomyelin. Through postulated effects on cell shedding (palmitoyl-sphingomyelin), inflammation (conjugated linoleate), and innate immunity (p-aminobenzoate), metabolites mediated the CRC association with Fusobacterium and Porphyromonas by 29% and 34%, respectively. Overall, palmitoyl-sphingomyelin correlated directly with abundances of Enterobacteriaceae (Gammaproteobacteria), three Actinobacteria and five Firmicutes. Only Parabacteroides correlated inversely with palmitoyl-sphingomyelin. Other lipids correlated inversely with Alcaligenaceae (Betaproteobacteria). Six Bonferroni-significant correlations were found, including low indolepropionate and threnoylvaline with Actinobacteria and high erythronate and an uncharacterized metabolite with Enterobacteriaceae.
  
  
  CONCLUSIONS
  Feces from CRC cases had very strong microbe-metabolite correlations that were predominated by Enterobacteriaceae and Actinobacteria. Metabolites mediated a direct CRC association with Fusobacterium and Porphyromonas, but not an inverse association with Clostridia and Lachnospiraceae. This study identifies complex microbe-metabolite networks that may provide insights on neoplasia and targets for intervention.
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, Maryland 20892-9704, United States of America.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Avenue, #518, New York, New York 10016, United States of America.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, Maryland 20892-9704, United States of America.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Sampson
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, Maryland 20892-9704, United States of America.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, Maryland 20892-9704, United States of America.
authors.forename: Guoqin
authors.initials: G
authors.lastname: Yu
authors.affiliation: Information Management Services, 6110 Executive Boulevard, Rockville, Maryland 20852,United States of America.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Avenue, #518, New York, New York 10016, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, Maryland 20892-9704, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000382:microbiology*; D005189:False Positive Reactions; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007422:Intestines / Q000382:microbiology; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015999:Multivariate Analysis