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Abstract Title: Microbial basis for methylmercury (MeHg) metabolism and elimination in humans.
Presenter Name: Matthew Rand
Company/Institution: University of Rochester
Session: Human Exposure and Risk Assessment of Hg
Day and Session: Tuesday 26th July - Session One
Start Time: 07:30 UTC
Co-Authors: Matthew Rand

Abstract Information :

Prevailing evidence implicates MeHg biotransformation (e.g. de-methylation) by gut microbes as a rate limiting step in elimination. However, the mechanism of MeHg de-methylation and the taxa responsible in the human gut microbiome remain unknown. We examined the relationship of variability in MeHg elimination to gut microbial biotransformation activity and community composition. Elimination rates were determined via longitudinal hair analysis of 27 volunteers following ingestion of tuna with known Hg content. Stool samples were used for crude culture MeHg biotransformation assays. Fecal DNA was used for metagenomic sequencing and bioinformatics analyses. MeHg elimination rates ranged from Kel = 0.008 to 0.023 day-1 (t1/2 = 30 to 89 days). The rate of MeHg biotransformation in stool cultures from each participant were significantly correlated with the individual?s elimination rate. Gut microbiome community composition was not strongly correlated with MeHg elimination rate. Metagenome assembled genomes (MAGs) were partitioned to create operational taxonomic units (OTUs) at the species level and comparisons revealed that the abundance of Alistipes onderdonkii positively correlated with MeHg elimination rate. To determine protein coding sequences likely involved in MeHg elimination, a comprehensive search for the well-known merA/merB MeHg demethylation genes was conducted first, however, homologs of these genes were not detected in any community. Clustered protein sequences that function in amino acid and carbohydrate metabolism were identified that positively and negatively correlate with MeHg elimination, respectively. Moreover, 3.3% of the proteins belonging to A. onderdonkii were positively correlated with MeHg elimination, which represented a greater proportion of proteins than that of any other microbiome OTU. Our results indicate non-merA/merB biotransformations of MeHg are responsible for biotransformation in the human body and that differences at the OTU level as opposed to those driving whole community diversity metrics (e.g. alpha- and beta-diversity) are more accurate indicators of MeHg biotransformation and elimination kinetics.

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