title: Enterolignan-producing phenotypes are associated with increased gut microbial diversity and altered composition in premenopausal women in the United States.
abstract: BACKGROUND
  Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure.
  
  
  METHODS
  We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40-45 years) women in the United States. Urinary enterolignans were measured using gas chromatography-mass spectroscopy. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression.
  
  
  RESULTS
  After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (P = 0.0007), or the diversity of the GMC (P = 0.01). The GMC associated with high ENL production was distinct (UNIFRAC, P < 0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp.
  
  
  CONCLUSIONS
  Diversity and composition of the GMC are associated with increased human exposure to enterolignans.
  
  
  CONCLUSIONS
  Differences in gut microbial diversity and composition explain variation in gut metabolic processes that affect environmental exposures and influence human health. Cancer Epidemiol Biomarkers Prev; 24(3); 546-54. ©2014 AACR.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. mhullar@fhcrc.org.
authors.forename: Meredith A J
authors.initials: MA
authors.lastname: Hullar
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington, Seattle, Washington.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Lancaster
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tseng
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Karlyn
authors.initials: K
authors.lastname: Beer
authors.affiliation: University of Bristol, Bristol, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Atkinson
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Wähälä
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Wade K
authors.initials: WK
authors.lastname: Copeland
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Randolph
authors.affiliation: Group Health Research Institute, Seattle, Washington.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Newton
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington, Seattle, Washington.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D000328:Adult; D015930:Diet Records; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology*; D006801:Humans; D017705:Lignans / Q000096:biosynthesis* / Q000378:metabolism; D064307:Microbiota; D008875:Middle Aged; D010641:Phenotype; D017697:Premenopause / Q000378:metabolism; D014481:United States
chemical_list: D017705:Lignans; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone