Irreversible effects of trichloroethylene on the gut microbial community and gut-associated immune responses in autoimmune-prone mice

J Appl Toxicol. 2019 Feb;39(2):209-220. doi: 10.1002/jat.3708. Epub 2018 Sep 5.


The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)-induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500 μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154 days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue-associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high-dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high-dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin-33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin-3, granulocyte-macrophage colony-stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.

Keywords: Bacteroidetes; Firmicutes; TCE; bacteria; gastrointestinal; immune; intestine; microbiome; toxicity; xenobiotic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / microbiology
  • Cytokines / immunology
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Ileum / drug effects*
  • Ileum / immunology
  • Ileum / microbiology
  • Immunity, Mucosal / drug effects
  • Maternal Exposure
  • Mice
  • Mice, Inbred Strains
  • Microbiota / drug effects*
  • Microbiota / immunology
  • Pregnancy
  • Trichloroethylene / toxicity*
  • Water Pollutants, Chemical / toxicity*


  • Cytokines
  • Water Pollutants, Chemical
  • Trichloroethylene