title: Triclosan and prescription antibiotic exposures and enterolactone production in adults.
abstract: BACKGROUND
  The gut microbiome plays an important role in the development of disease. The composition of the microbiome is influenced by factors such as mode of delivery at birth, diet and antibiotic use, yet the influence of environmental chemical exposures is largely unknown. The antimicrobial compound triclosan, found in many personal care products and widely detected in human urine, is an environmental exposure for which systemic microbiotic effects may be of particular interest. To investigate the relationship between triclosan and gut microflora, we assessed the association between triclosan and enterolactone, an intestinal metabolite that is produced via bacterial transformation of dietary lignans (seeds, nuts) and has known susceptibility to oral antibiotics.
  
  
  METHODS
  We examined urinary triclosan and enterolactone for 2005-2008 U.S. National Health and Nutrition Examination Survey subjects, aged ≥20 years (n=3041). We also examined the association between prescription antibiotic use and enterolactone to confirm its susceptibility to changes in bacterial composition of the body. Associations between natural log-transformed enterolactone and (1) detected vs. not detected (<2.3 ng/mL) triclosan, (2) triclosan quintiles (Q1-Q5), and (3) any vs. no antibiotics were estimated with multiple linear regression, adjusting for sex, age, race, body mass index, poverty income ratio, education, fiber intake, bowel movement frequency, cotinine and creatinine (n=2441).
  
  
  RESULTS
  Triclosan was detected in 80% of subjects (range: <2.3-3620 ng/mL), while enterolactone was detected in >99% of subjects (range: <0.1-122,000 ng/mL). After adjustment, enterolactone was not associated with triclosan (detect vs. non-detect: β= 0.07 (95% CI: -0.15, 0.30); Q5 (≥104.5 ng/mL) vs. Q1 (none): β= 0.06 (95% CI: -0.21, 0.34)). In sex-stratified analyses, triclosan was associated with higher enterolactone in women (detect vs. non-detect: β= 0.31 (95% CI: -0.07, 0.70), but not men β= -0.18 (95% CI: -0.47, 0.11). However, any antibiotic use (n=112), as compared to no antibiotic use, was associated with significantly lower enterolactone (β=-0.78 (95%CI: -1.22, -0.36)), with no sex-specific effects. This association was driven by inverse associations with the following antibiotic classes: macrolide derivatives, quinolones, sulfonamides, and lincomycin derivatives.
  
  
  CONCLUSIONS
  Antibiotics, but not triclosan, are negatively associated with urinary enterolactone. Antibiotics may reduce enterolactone by killing certain gut bacteria. At levels detected in the U.S., triclosan does not appear to be acting similarly, despite broad antimicrobial properties. Additional study of determinants of triclosan exposure and enterolactone production may be needed to better understand positive associations among women.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, P.O. Box 12233 Research Triangle Park, NC 27709, USA. Electronic address: margaret.adgent@nih.gov.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Adgent
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, P.O. Box 12233 Research Triangle Park, NC 27709, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Rogan
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000652:urine; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017705:Lignans / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D055553:Prescription Drugs; D014260:Triclosan / Q000009:adverse effects* / Q000652:urine; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017705:Lignans; D055553:Prescription Drugs; D014260:Triclosan; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone
keywords: Antimicrobial; Enterolactone; Intestinal metabolite; NHANES; Triclosan