Lead exposure changes carbohydrate and amino acid metabolism corresponding to a disturbed microbiota-gut-brain axis in mice

Chronic lead exposure can cause irreversible neurological damage. The brain-gut axis's involvement in lead-induced neurotoxicity, a key factor in cognitive deficits, requires further exploration. To deepen our understanding of how lead exposure influences the brain-gut connection, we carried out the behavioral and morphological analysis, as well as metabolome and metagenome analysis associated with the gut-brain axis. The study results suggested that Pb exposure resulted in inflammation in both the brain and gut, along with decreased cognitive ability. The metagenomic data indicated that Pb exposure impacted microbial diversity and composition, with a marked increase in genes linked to carbohydrate and amino acid metabolism. Compared to control mice, the metabolic profiles of brain, feces and serum samples from Pb-exposed mice were differed, with higher levels of amino acids in serum and soluble sugars in feces, but lower levels of amino acids in brain. Key enriched microbial (eg: Tenericutes, Thermotogae, Alistipes_putredinis) was significantly negatively correlated with brain amino acid (eg: proline, asparagine, tryptophan) but positively correlated with serum amino acids (eg: valine, leucine, tyrosine). This research uncovers new perspectives on how lead exposure alters metabolites in the brain-gut axis, regulated by gut microbiota, highlighting the need for additional research on lead's health risks.