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

The human gut is populated by up to 100 trillion (1014) 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): 0.057 g/g

Average Hair THg levels were >20 times lower than US reference dose (1.2 g/g)

Hair THg (g/g)

Fre

qu

ency

Average Hair Total Mercury (THg): 0.057 g/g

Average Hair THg levels were >20 times lower than US reference dose (1.2 g/g)

Fre

qu

ency 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)

Fre

qu

ency

Percent MeHg (of THg): <1-5.8%

Log

10 S

tool

MeH

g (p

g/g)

Log10 Stool THg (ng/g)

Stool MeHg content was positively correlated with stool THg content (non-significant)

r-squared=0.06p=0.33

Log

10 S

tool

MeH

g (p

g/g)

Trimester 1 BMI (kg/m2)

Stool MeHg content was inversely correlated with trimester 1 Body Mass Index (BMI) (non-significant)

r-squared=0.09p=0.25

Log

10 S

tool

MeH

g (p

g/g)

Log10 Cord Blood MeHg (g/L)

Stool MeHg content was positively correlated with cord blood MeHg (non-significant)

r-squared=0.33p=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 StaffUSC Department of Environmental Health Sciences

Students/postdocs: Chuan Hong for help with hair THg and MeHg analysesSi Chen for help with stool MeHg analyses

Thank you!!!!