Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota

Polyhalogenated carbazoles (PHCZs) have been widely accepted as emerging pollutants, whereas their ecological and health risks remain uncertain. Herein, female and male Sprague-Dawley (SD) mice were treated with four typical PHCZs to investigate their nega-tive consequences, along with alternations in gut microbiota to indicate underlying mecha-nisms. In female mice, the relative liver weight ratio increased after four PHCZs exposure; 2-bromocarbazole (2-BCZ) increased urine glucose level; 3-bromocarbazole (3-BCZ) decreased the glucose and total cholesterol levels; 3,6-dichlorocarbazole (3,6-DCCZ) decreased glucose level. The only disturbed biochemical index in male mice was the promoted alkaline phos-phatase (ALP) level by 3,6-DCCZ. We also found that the differential blood biochemical in-dices were correlated with gut microbiota. 3-BCZ and 3,6-DCCZ altered Bacteroidetes and Pro-teobacteria phyla in female and male mice, which were correlated with metabolic disorders. Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity and metabolic disorders may be due to their dioxin-like potentials and endocrine disrupting activities, and the gender differences might result from their estrogenic activities. Overall, data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms. (c) 2022 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study investigated the negative consequences of polyhalogenated carbazoles (PHCZs) on mice and the alterations in gut microbiota. The results revealed that PHCZs may induce hepatotoxicity and metabolic disorders, which could be attributed to their dioxin-like potentials and endocrine disrupting activities. Furthermore, gender differences were observed in the effects of PHCZs on mice.