Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma, and breast milk; with detection limits generally in the pg-ng mL−1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability for large-scale exposomics-type cohort studies.
Exposure to man-made and natural chemicals is a major, yet not sufficiently considered, environmental risk factor in the etiology of chronic diseases. Current human biomonitoring approaches typically measure a limited number of exposures rather than investigating complex mixtures. The latter would be fundamental and necessary for a holistic assessment of chemical exposure in exposome-wide association studies. In this work, an highly-sensitive liquid chromatography-tandem mass spectrometry approach was developed and thoroughly-validated. The assay enables the simultaneous and targeted assessment of more than 80 highly-diverse xenobiotics in the investigated body fluids of urine, serum/plasma, and breast milk; the detection limit for most toxicants are in the pg-ng/mL range. In the plasma of extremely-premature infants (gestational age <28 weeks, birth weight <1 kg) a total of 27 different xenobiotics are identified; including severe contamination with synthetic plasticizers, perfluorinated alkylated substances and parabens. In an independent sample set of breast milk that was longitudinally collected over the first 211 days post-partum, a total of 29 analytes is detected, including the first-ever identification of pyrrolizidine- and tropane alkaloids in this matrix. Based on the generated data, a preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, our proof-of-principle experiments show significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability in future large-scale exposomics-type cohort studies in vulnerable populations.
The gut microbiome has been associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigated the longitudinal fecal and plasma metabolome of 51 extremely premature infants using LC-HRMS-based untargeted metabolomics. This was expanded by an investigation of bile acids and amidated bile acid conjugates in feces and plasma by LC-MS/MS-based targeted metabolomics. The resulting data was integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor and T-cell profiles. We identified an early onset of differentiation in neuroactive metabolites and bile acids between infants with and without brain injury. We detected several bacterially-derived bile acid amino acid conjugates and secondary bile acids in the plasma already three days after delivery, indicating the early establishment of a metabolically active gut microbiome. These results give new insights into the early life metabolome of extremely premature infants.
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