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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. [Display omitted] • Daily exposure doses of antibiotic were estimated from urinary concentrations in 4247 adults. • Urinary bile acids and their ratios were used to reflect bile acid homeostasis. • A cumulative EDED of antibiotics below the safety threshold was observed in 91.8% of adults. • Antibiotic EDED was significantly associated with urinary bile acids and their ratios. • The lowest EDED disturbing bile acid homeostasis may be well below the safety threshold. [ABSTRACT FROM AUTHOR]

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms. • Early postnatal PM2.5 exposure induced more pronounced ASD-like phenotype in male offspring rats than maternal exposure. • Early postnatal period may be a sensitive window for PM2.5 to trigger autism spectrum disorder development. • PM2.5 exposure caused neuroinflammation and reduced anti-inflammatory melatonin levels in offspring rat brains. • PI3K-AKT pathway activation may link developmental PM2.5 exposure and autism spectrum disorder pathogenesis. [ABSTRACT FROM AUTHOR]