Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity.
Level 4 - case-series / case-control
Cross-sectional human observational study combined with an animal mechanistic experiment
PubMed 38522229 · doi:10.1016/j.envint.2024.108569
What was done
Researchers evaluated 264 Danish adults (121 men and 143 women, mean age 56.6 ± 7.3 years, mean BMI 29.7 ± 6.0 kg/m²) to assess relationships between environmental toxicant exposure, the gut microbiome, bile acids, and metabolic health. Serum levels of per- and polyfluoroalkyl substances (PFAS) and 27 other environmental toxicants along with bile acids were measured using mass spectrometry. Gut microbiota were profiled via whole-genome shotgun sequencing of stool samples, and personalized genome-scale metabolic models were built to model bile acid pathways. In silico causal mediation was tested, and findings were compared against an experimental model of perfluorooctanoic acid (PFOA) exposure in PPARα-humanized mice.
What was found
Serum concentrations of 12 environmental toxicants were associated with obesity and insulin resistance. High toxicant exposure was linked to increased abundance of bacterial species across 13 genera (including Anaerotruncus, Alistipes, Bacteroides, and Escherichia), predominantly in men, while highly exposed females showed reduced abundance of Prevotella copri. High toxicant levels correlated with elevated lithocholic acid (LCA) and reduced ursodeoxycholic acid (UDCA). In silico modeling and the mouse exposure experiment supported microbial secondary bile acid disruption as a potential mediator. Specific effect sizes, correlation coefficients, and p-values were not reported in the abstract.
Why it matters
This study provides evidence linking environmental chemical exposures to obesity and insulin resistance through alterations in the gut microbiome and host secondary bile acid metabolism.
Limits
The human cohort design is cross-sectional, preventing determination of causality or direction of effect in humans. The study sample was limited to middle-aged Danish adults, and exact statistical estimates and effect magnitudes were omitted from the abstract.
Cited by
- supports PFAS exposure is linked to major health issues including hormone disruption, gut microbiome disruption, and fertility problems.
- supports Per- and polyfluoroalkyl substances (PFAS) are linked to endocrine disruption, gut microbiome disruption, and fertility issues.