Tributyltin (TBT), an
environmental pollutant widely used in antifouling coatings, can cause multiple-organ toxicity and gut microbiome
dysbiosis in organisms, and can even cause changes in the host metabolomic profiles. However, little is known about the underlying effects and links of TBT-induced metabolic changes and gut microbiome
dysbiosis. In this study, rats were exposed to TBT at a dose of 100 μg kg-1
body weight (BW) for 38 days, followed by multi-omics analysis, including microbiome, metabolomics, and metallomics. Results showed that TBT exposure reduced rat
weight gain and decreased the serum
triglyceride (TG) level. Metabolic analysis revealed that TBT fluctuated
linoleic acid metabolism and
glycerophospholipid metabolism in the liver; the tricarboxylic acid cycle (TCA cycle),
nicotinate and
nicotinamide metabolism, and
arachidonic acid metabolism in serum;
glycine,
serine, and
threonine metabolism, the one
carbon pool by
folate,
nicotinate, and
nicotinamide metabolism; and
tryptophan metabolism in feces. Furthermore, TBT treatment dictated liver
inflammation due to enhancing COX-2 expression by activating
protein kinase R-like ER
kinase (PERK) and
C/EBP homologous protein (CHOP) to induce endoplasmic reticulum (ER) stress instead of stimulating
arachidonic acid metabolism. Meanwhile, alteration of the intestinal flora [Acetivibrio]_ethanolgignens_group, Acetatifactor, Eisenbergiella, Lachnospiraceae_UCG-010, Enterococcus, Anaerovorax, and Bilophila under TBT exposure were found to be involved in further mediating liver
inflammation, causing lipid metabolism abnormalities, such as TG,
linoleic acid, and
glycerophospholipids, and interfering with the energy supply process. Among these, [Acetivibrio]_ethanolgignens_group, Enterococcus, and Bilophila could be considered as potential
biomarkers for TBT exposure based on receiver operator characteristic (ROC) curve analysis.