Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice

Karen Chiu,Maria De Godoy,Jodi Flaws,Jessica Gutierrez,Shah Bashir,Liying Gao,Isaac Cann,Romana Nowak,Christopher Fields,Jenny Drnevich

doi:10.3390/toxics9090215

Karen Chiu, Maria De Godoy + Show 8 more

Open Access

https://doi.org/10.3390/toxics9090215

Copy DOI

Abstract

Di-2-ethylhexyl phthalate (DEHP) is a plasticizer commonly found in polyvinyl chloride, medical equipment, and food packaging. DEHP has been shown to target the reproductive system and alter the gut microbiome in humans and experimental animals. However, very little is known about the impact of DEHP-induced microbiome changes and its effects during pregnancy. Thus, the objective of this study was to investigate the effects of DEHP exposure during pregnancy on the cecal microbiome and pregnancy outcomes. Specifically, this study tested the hypothesis that subacute exposure to DEHP during pregnancy alters the cecal microbiome in pregnant mice, leading to changes in birth outcomes. To test this hypothesis, pregnant dams were orally exposed to corn oil vehicle or 20 µg/kg/day DEHP for 10 days and euthanized 21 days after their last dose. Cecal contents were collected for 16S Illumina and shotgun metagenomic sequencing. Fertility studies were also conducted to examine whether DEHP exposure impacted birth outcomes. Subacute exposure to environmentally relevant doses of DEHP in pregnant dams significantly increased alpha diversity and significantly altered beta diversity. Furthermore, DEHP exposure during pregnancy significantly increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes and Deferribacteres compared with controls. The affected taxonomic families included Deferribacteraceae, Lachnospiraceae, and Mucisprillum. In addition to changes in the gut microbiota, DEHP exposure significantly altered 14 functional pathways compared with the control. Finally, DEHP exposure did not significantly impact the fertility and birth outcomes compared with the control. Collectively, these data indicate that DEHP exposure during pregnancy shifts the cecal microbiome, but the shifts do not impact fertility and birth outcomes.

Highlights

IntroductionPhthalates are plasticizers commonly added to polyvinyl chloride to create soft and malleable plastics
Identification of functional pathways significantly altered by Di-2-ethylhexyl phthalate (DEHP) exposure show that DEHP could impact the whole-body system, but these functional changes need to be studied in detail to gain insight and truly understand the impact of this environmental toxicant on microbial community diversity, dynamics, and function, and their impact on the host
One of the major limitations of this study is the lack of information on whether the observed functional changes in the gut were apparent in the reproductive organs, such as the ovaries and uterus

Summary

Introduction

Phthalates are plasticizers commonly added to polyvinyl chloride to create soft and malleable plastics. These chemicals are stabilizers for many solvents to retain color and creativecommons.org/licenses/by/ 4.0/). Phthalates can be found in children’s toys, clothing (faux leather or printed vinyl materials on clothes), personal care products (nail polish, lotion, deodorants, perfumes, and shampoo), medical equipment (blood bags and tubing), and housing materials (vinyl flooring, carpets, and shower curtains). Humans are exposed to DEHP through ingestion, inhalation, and dermal absorption, with ingestion being the most common route of exposure. Intravenous absorption of DEHP is another common route of exposure in specific populations, such as patients on dialysis, tube feedings, or intravenous infusions [4,5]

Objectives

Methods

Results

Discussion

Conclusion