Lead promoted bile acid deconjugation by modulating gut bacteria encoding bile salt hydrolase (BSH) in Rana chensinensis tadpoles

Abstract

Bile salt hydrolase (BSH) is produced by gut bacteria and is responsible for deconjugating amino acids from the aliphatic side chains of conjugated bile acids (BAs), initiating the critical first step in BAs metabolism. Lead (Pb) is known to cause gut microbial dysbiosis, but whether it affects BAs profiles by reshaping the gut microbiota remains elusive. Here, using targeted BAs metabolomics and metagenomics sequencing, we found that 200 μg/L Pb treatment led to a significant increase in the abundance of BSH-producing microbiota (e.g., Eubacterium and Yersinia), thus promoting the deconjugation of taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). Consequently, the accumulation of relatively hydrophobic BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) may cause damage to enterocytes (e.g., reduced microvilli and enterocyte heights), which attenuated tadpole digestion and ultimately led to significant reductions in morphological parameters. The inhibition of tadpole growth by Pb toxicity may negatively affect their survival and even increase their risk of death. Overall, these results revealed for the first time the toxicological mechanism by which Pb reshapes the gut microbiota and thus disrupts the BAs profile, shedding new insights into the detrimental effects of Pb toxicity on amphibian growth.