Mercury Metabolism by Bacteria in Humans
Condition: Mercury--Toxicology
Study type: Interventional

Summary: 
      The purpose of this study is to evaluate how the bacteria in your gut can improve the
      break-down and de-toxification of non-harmful levels of a naturally occurring form of mercury
      (methylmercury) that comes with eating fish. This research could help scientists and doctors
      understand whether or not mercury in fish that we are likely to eat poses any concern for the
      health of people.
    

Detailed description: 
      The overall objective of this study is to investigate the role of gut microbes in mediating
      how humans metabolize and excrete the environmental neurotoxicant methylmercury (MeHg).
      Exposure to MeHg through consumption of fish continues to pose a health risk for many
      populations globally. There remains considerable uncertainty in advising the public on
      mercury risks associated with fish consumption. A great deal of uncertainty stems from the
      fact that the MeHg metabolism and elimination rate is known to vary widely from individual to
      individual. This translates into the possibility that two individuals consuming the same
      amount of fish with the same frequency could, unknowingly, experience as much as 4-fold
      difference in accumulation of MeHg in their bodies. Thus, there is a need for greater
      understanding of the mechanisms of MeHg metabolism and elimination, as well as for
      development of tools to assess these characteristics in people. Our scientific premise is
      that symbiotic microbes in the human gut are required for the efficient biotransformation
      (demethylation) and excretion of toxic MeHg. In this prospective intervention study we will
      examine the variation in the rate at which MeHg is excreted, both between human subjects and
      within subjects over time, and relate it to the MeHg demethylation activity that is harbored
      in their respective gut microbes. Furthermore, through intervention with a prebiotic dietary
      supplement, we will induce a change in the gut microbial composition within the same
      individual and evaluate if slower of faster MeHg metabolism ensues. With these approaches we
      will obtain gut microbiome samples that correlate with faster or slower MeHg elimination
      kinetics. We then aim to identify specific genera and species of bacteria in the human gut
      responsible for MeHg metabolism. We will do this by feeding volunteers fish meals with
      documented trace levels of MeHg that are below any harmful level of exposure. We will
      subsequently measure kinetic rates of MeHg elimination via mass-spectrometry analysis of hair
      strands. We will also sample feces from the subjects as a source of the gut microbiota and as
      a medium to analyze the extent of MeHg metabolism (demethylation) that parallels its
      elimination. Study team members at Montana State University will directly examine the ability
      of the human gut microbiota to induce MeHg metabolizing activity in germ-free mice at rates
      that correspond with that seen in the human subject it was derived from. In parallel, we will
      use metagenomic sequence-informed strategies to bring isolated strains of the human gut
      bacteria to culture and subsequently interrogate their MeHg demethylating activity. We
      anticipate our results will lead to a clearer understanding of the microbial basis of human
      MeHg metabolism.
    

Intervention name(s): Tuna fish; prebiotic
Intervention type(s): Other; Dietary Supplement
Intervention description(s): Six meals of tunafish (~200gms) will be consumed. Three meals will be consumed in a period of 14 days, and a subsequent 3 meals will be consumed within a 14 day period six month after the first 3 meals.; Prebiotin brand prebiotic will be consumed at 8grms/day for a period of 75 days. The prebiotic administration will begin with the second grouping of 3 fish meals.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science