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Updated: Aug 17, 2025
Assessing Hepatic Metabolic Changes During Progressive Colonization of Germ-free Mouse by 1H NMR Spectroscopy
Published on: December 15, 2011
Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota
Chenyang Ji1, Yunkai Luo2, Jiawen Yang3
1Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou 310015, China.
Abstract:
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 negative consequences, along with alternations in gut microbiota to indicate underlying mechanisms. 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 phosphatase (ALP) level by 3,6-DCCZ. We also found that the differential blood biochemical indices were correlated with gut microbiota. 3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria 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.
Insights
Polyhalogenated carbazoles (PHCZs) pose risks, impacting liver and metabolic health, with gut microbiota alterations. Gender differences in effects were observed, possibly due to estrogenic activity.
Area of Science:
- Environmental Science
- Toxicology
- Microbiology
Background:
- Polyhalogenated carbazoles (PHCZs) are emerging pollutants with unknown ecological and health risks.
- Understanding the toxicological effects and mechanisms of PHCZs is crucial for risk assessment.
Purpose of the Study:
- To investigate the adverse effects of four typical PHCZs on Sprague-Dawley (SD) mice.
- To explore the role of gut microbiota alterations in mediating PHCZ toxicity.
- To identify potential gender-specific differences in PHCZ toxicity and underlying mechanisms.
Main Methods:
- Exposure of female and male SD mice to four typical PHCZs.
- Analysis of blood biochemical indices, including liver weight ratio, glucose, total cholesterol, and alkaline phosphatase (ALP).
- Gut microbiota profiling to identify alterations in bacterial phyla (e.g., Bacteroidetes, Proteobacteria).
Main Results:
- PHCZ exposure increased relative liver weight in female mice.
- Specific PHCZs altered glucose and cholesterol levels in female mice, and ALP in male mice.
- PHCZs induced significant changes in gut microbiota composition, correlating with metabolic disorders and potentially explaining observed toxicity.
Conclusions:
- PHCZs can induce hepatotoxicity and metabolic disorders, possibly via dioxin-like and endocrine-disrupting activities.
- Observed gender differences in PHCZ toxicity may be linked to estrogenic activities.
- Gut microbiota alterations play a role in PHCZ-induced toxicity, providing insights into mechanisms of action.
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