The Influence of Gut Microbiota on the Speciation & Toxicity of Mercury During Pregnancy:

1. The Influence of Gut Microbiota on the Speciation & Toxicity of Mercury During Pregnancy: Results from a Feasibility Pilot Sarah E. Rothenberg1 and Sharon Keiser2 1USC Department of Environmental Health Sciences, 2Greenville Health System, Department of Obstetrics and Gynecology March 21, 2014

2. The human gut is populated by up to 100 trillion (1014) microbes, with a vast majority in the distal gut

3. Gut ecology differ between life-stages, including early/late pregnancy References: Biagi et al., 2010; Koenig et al., 2011; Koren et al., 2012

4. For mercury (Hg), speciation determines toxicity Inorganic Hg is less toxic than methylmercury (MeHg). MeHg is a neurotoxin, that crosses the placental barrier. Hg methylation and MeHg demethylation are microbially-mediated processes, and are both important in the gut. References: Clarkson & Magos, 2006; Parks et al., 2013; Rowland, 1995

5. Hypothesis: Shifts in gut microbiota during pregnancy will influence prenatal MeHg exposure. Approach: In fall 2013, in collaboration with Greenville Health System (OB/GYN), complete a feasibility pilot including measurement of MeHg in maternal hair and stool samples, and cord blood samples.

6. FEASIBILITY PILOT • Pregnant women (36-39 wk gestation) were recruited • Approx. 40 women were interviewed, 19 provided informed consent • 17 mothers provided both hair and stool samples • Cord blood was collected at parturition (n=7)

7. Average Hair THg levels were >20 times lower than US reference dose (1.2 g/g) Average Hair Total Mercury (THg): 0.057 g/g Frequency Hair THg (g/g)

8. Average Hair THg levels were >20 times lower than US reference dose (1.2 g/g) Average Hair Total Mercury (THg): 0.057 g/g EPA reference dose: 1.2 g/g Frequency Hair THg (g/g)

9. However, in the absence of dietary MeHg exposure, stool MeHg content was measurable Percent MeHg (of THg): <1-5.8% Frequency Stool MeHg (pg/g)

10. Stool MeHg content was positively correlated with stool THg content (non-significant) r-squared=0.06 p=0.33 Log10 Stool MeHg (pg/g) Log10 Stool THg (ng/g)

11. Stool MeHg content was inversely correlated with trimester 1 Body Mass Index (BMI) (non-significant) r-squared=0.09 p=0.25 Log10 Stool MeHg (pg/g) Trimester 1 BMI (kg/m2)

12. Stool MeHg content was positively correlated with cord blood MeHg (non-significant) r-squared=0.33 p=0.18 Log10 Stool MeHg (pg/g) Log10 Cord Blood MeHg (g/L)

13. Future work (among a larger cohort): • Verify whether MeHg production in the gut results in higher prenatal MeHg exposure • Address whether shifts in gut microbiota between 1rst and 3rd trimesters are associated with changes in net MeHg production • Determine the dietary sources of inorganic Hg that promote Hg methylation in the gut.

14. ACKNOWLEDGEMENTS Greenville Health System OB/GYN Research Staff USC Department of Environmental Health Sciences Students/postdocs: Chuan Hong for help with hair THg and MeHg analyses Si Chen for help with stool MeHg analyses

15. Thank you!!!!