TY - JOUR
T1 - Impact of low-level exposure to antibiotics on bile acid homeostasis in adults
T2 - Implication for human safety thresholds
AU - Wang, Yuanping
AU - Wang, Yi
AU - Zhao, Qi
AU - Cong, Wenjuan
AU - Wang, Na
AU - Zhao, Ke
AU - Liu, Jiaqi
AU - Liu, Xiaohua
AU - Zhao, Genming
AU - Lambert, Helen S
AU - Huang, Min
AU - Wang, Hexing
AU - Chen, Yue
AU - Jiang, Qingwu
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.
AB - Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.
U2 - 10.1016/j.ecoenv.2024.116451
DO - 10.1016/j.ecoenv.2024.116451
M3 - Article (Academic Journal)
C2 - 38759535
SN - 0147-6513
VL - 279
JO - Ecotoxicology and environmental safety
JF - Ecotoxicology and environmental safety
M1 - 116451
ER -