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

The human gut is populated by up to 100 trillion (10 14 ) microbes, with a vast majority in the distal gut

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

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 For mercury (Hg), speciation determines toxicity

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.

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) FEASIBILITY PILOT

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

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

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

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

Log 10 Stool MeHg (pg/g) Trimester 1 BMI (kg/m 2 ) Stool MeHg content was inversely correlated with trimester 1 Body Mass Index (BMI) (non-significant) r-squared=0.09 p=0.25

Log 10 Stool MeHg (pg/g) Log 10 Cord Blood MeHg (  g/L) Stool MeHg content was positively correlated with cord blood MeHg (non-significant) r-squared=0.33 p=0.18

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.

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

Thank you!!!!