Toxic effects of DEHP and MEHP on gut-liver axis in rats via intestinal flora and metabolomics
Jiaqi Wang,
Hongwei Liu,
Xiwen Kou,
Yuxin Zhang,
Yang Wang,
Changlan Chen,
Zheng Xiang,
Xin Wang,
Ce Su,
Yangcheng Liu
Affiliations
Jiaqi Wang
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
Hongwei Liu
Liaoning Cancer Hospital & Institute, Shenyang, China
Xiwen Kou
College of Foreign Languages, Northeastern University, Shenyang, China
Yuxin Zhang
School of Pharmaceutical Science, Liaoning University, Shenyang, China
Yang Wang
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
Changlan Chen
School of Pharmaceutical Science, Liaoning University, Shenyang, China
Zheng Xiang
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
Xin Wang
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China
School of Pharmaceutical Science, Liaoning University, Shenyang, China; Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China; Corresponding author
Summary: Di (2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor and commonly used as a plasticizer. Exposure to DEHP and its active metabolite mono-2-ethylhexyl phthalate (MEHP) can lead to adverse health consequences; however, the toxic mechanism is remains unclear. In this research, male and female rats were exposed to DEHP and MEHP by oral gavage for 60 consecutive days. Pathological analysis revealed that DEHP and MEHP exposure could affect liver, heart, kidney, and testis tissues, as well as alter biochemical indicators. Metagenomics (16S rRNA gene sequencing) analysis indicated that DEHP and MEHP could reduce the diversity and alter the composition of the gut microbiota. Toxic exposure also affected the levels of short chain fatty acids (SCFAs), with noticeable variations between genders. Metabolomic analysis revealed that DEHP and MEHP could influence bile acids, amino acids, hormones, and lipids. These results demonstrate that exposure to DEHP and MEHP can induce toxicity in rats via the gut-liver axis.
