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

Abstract

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.

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

“…Despite involvement of several environmental agents in the pathogenesis of ADs (7), very little is known on their impact to microbiota and the role of subsequent dysbiosis on disease initiation/progression. TCE exposure, which is known to induce/exacerbate SLE in both experimental animals and humans, is also reported to cause alterations in the gut microbiome with increased abundance of genus Bifidobacterium and bacterial family Enterobacteriaceae as well as lower abundance of the genus Bacteroides and Lactobacillus in MRL+/+ mice at a high but occupationally relevant TCE dose compared to controls (100). Smoking affects the microbiome composition in animal models and humans.…”

Sex-Dependent Effects on Liver Inflammation and Gut Microbial Dysbiosis After Continuous Developmental Exposure to Trichloroethylene in Autoimmune-Prone Mice

“…Several gut cytokines in female MRL +/+ mice developmentally exposed to TCE were altered. This included decreases in IL-3, Eotaxin, GM-CSF, and IFN-γ ( Blossom et al, 2018 ; Khare et al, 2019 ), and an increase in KC ( Khare et al, 2019 ). Unexpectedly, these differences were more apparent in males rather than females, and treatment related effects were only observed in males except for GM-CSF, where treatment related decreases were observed in both sexes.…”

“…Developmental TCE exposure was associated with decreased microbial abundance and a shift in microbial phyla [( Bacteroidetes to Firmicutes ; ( Blossom et al, 2018 ). Exposure to TCE during the developmental stage similarly had irreversible effects (i.e., after TCE removal during adulthood) on the gut microbial community and gut-associated immune response in adult MRL mice ( Khare et al, 2019 ). In our model of TCE-induced AIH in lupus-prone female mice, CD4 cells infiltrated the liver leading to a cascade of inflammatory events that are counter balanced by increased IL-6 signaling.…”

L-Theanine: Neuroprotective against Trichloroethylene-induced Parkinsons disease hallmarks

“…TCE has also become a prevalent air pollutant (Doherty, 2000). In accordance with Braak's hypothesis, TCE-induced PD is hypothesized to progress in living organisms through the ingestion of TCEcontaminated drinking water and inhalation of TCEcontaminated air through the gastrointestinal and olfactory tract, respectively Khare et al, 2018;Rietdijk et al, 2017;Yulug et al, 2019). More importantly, TCE is also able to infiltrate the blood-brain barrier (BBB) allowing for accelerated neurodegeneration and PD onset (Bonvallot et al, 2010).…”