Lead exposure exacerbates adverse effects of HFD on metabolic function via disruption of gut microbiome, leading to compromised barrier function and inflammation.

Purpose: The toxicity of lead (Pb) has been intensively studied, while the adverse effects in the population on a high-fat diet (HFD) remain unclear. This study compared the different biologic effects of Pb in CHOW and HFD-fed mice and investigated the important role that gut microbiota may play.

Methods: C57BL/6 mice were fed a CHOW diet and HFD with or without 1 g/L Pb exposure through drinking water for 8 weeks. Using oral glucose tolerance test, histopathological observation, real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay, and 16S high-throughput sequencing to compare the Pb toxicity, fecal microbiota transplantation was conducted to investigate the key role of gut microbiota.

Results: The metabolic disorders induced by HFD were aggravated by chronic Pb intake, and HFD exacerbated the Pb accumulation in the colon by 96%, 32% in blood, 27% in the liver, and 142% in tibiae. Concomitantly, Pb induced more serious colonic injury, further disturbing the composition of gut microbiota in the HFD-fed mice. Moreover, altered fecal microbiota by HFD and Pb directly mediated metabolic disorders and colonic damage in recipient mice, which emphasized the importance of gut microbiota.

Conclusion: These findings indicated that the population with HFD has lower resistance and would face more security risks under Pb pollution, and pointed out the importance of assessing the health impacts of food contaminants in people with different dietary patterns.