Gestation and lactation triphenyl phosphate exposure disturbs offspring gut microbiota in a sex-dependent pathway

• Published in: Food and chemical toxicology Vol. 172; p. 113579
• Main Authors: Liu, Xiaoshan, Lin, Juntong, Chen, Yuting, Jiang, Mengzhu, Liu, Qian, Zhang, Jing, Lu, Xiaoxun, Hong, Jiabin, Sun, Wenjing, Sun, Yanqin, Guo, Lianxian
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2023
• Subjects: Animals; Female; Gastrointestinal Microbiome; Gut microbiota; Gut-liver axis; Lactation; Liver; Male; Mice; Organophosphates - metabolism; Organophosphates - toxicity; Pregnancy; Sexually dimorphic; Triphenyl phosphate; Gut microbiota; Triphenyl phosphate; Sexually dimorphic; Gut-liver axis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2022.113579

Triphenyl phosphate (TPhP) is an Organophosphate flame retardant (OPFR) that has been widely used in many commercial products. Following its widely usage, its health risk has been concerned. In this study, mice were exposed to TPhP (1 mg/kg) during pregnancy and lactation (E0-PND21), the effect of TPhP on gut microbiota and its role in TPhP mediated lipid metabolism disturbance of offspring was investigated. Our results showed that TPhP disturbed the gut microbiota in dam or offspring at different extent, with male offspring experiencing major effects. Both the composition, abundance or network of gut microbiome was affected in male offspring. In male offspring, expression of genes along gut-liver axis including FXR, CYP7A1, SREBP-1c and ChREBP was significantly up-regulated, and expression of SHP, FGF15 and ASBT was significantly down-regulated. Consistent with this, lipid accumulation in the liver, and increased level of triglyceride, total cholestrol and total bile acid in the serum was observed. The changed abundance of Ruminococcaceae, Clostridiaceae, and Bacteroidaceae shows strong correlation with disturbed lipid metabolism in male offspring. Our research showed that indirect TPhP exposure during early life stage could affect the gut microbiota and gene expression along gut-liver axis in offspring at sex-dependent pathways, with males experiencing more effects.
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•Gestational and lactational TPhP exposure disturbs gut microbiota in mice, with male offspring expericing major effects.•TPhP disturbs expression of genes along gut-bile acid-liver axis at sex dimorphic pattern.•TPhP induces lipid accumulation in the liver of male offspring.•The disturbance of Ruminococcaceae, Clostridiaceae and Bacteroidaceae were significantly correlated with changed lipid metabolism.