Elemicin exposure induced aberrant lipid metabolism via modulation of gut microbiota in mice

Elemicin (Ele) is a constituent of natural alkenylbenzene present in many foods and herbs. Ele exposure could induce hepatomegaly and hepatosteatosis. However, the role of gut microbiota in Ele-induced hepatotoxicity remains unclear. Here, the mice were treated with 200 mg/kg/day of Ele for 4 weeks with or without depletion of gut microbiota by antibiotics cocktail treatment. The mice treated with Ele showed enlargement of liver and slight hepatosteatosis, accompanied by higher levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG). Ele could also shift the structure of fecal microbiota and increase the richness. Functional prediction of the microbiota revealed the enrichment of non-alcoholic fatty liver disease pathway upon Ele exposure. Compared with control group, Patescibacteria and Epsilonbacteraeota were significantly enriched at the phylum level upon Ele treatment. A total of 20 genera were significant with respect specifically to Ele exposure, including decreased Alistipes and elevated Ruminiclostridium_9 and Gordonibacter. Among them, 13 retained significant associations with ALT and TG by Spearman correlation test, 4 were correlated with AST. Further MaAsLin analysis revealed that ALT was associated with 4 differentially abundant genera, such as Alistipes and Ruminiclostridium_9 and Gordonibacter. In addition, only Alistipes was significantly correlated with serum TG. Intriguingly, depletion of the microbiota significantly attenuated hepatosteatosis, restore increased ALT, AST and TG and inhibit the expression of genes involved in de novo lipogenesis and adipocyte differentiation, such as Fasn, ADIPOQ and leptin. Collectively, depletion of gut microbiota protected against Ele induced aberrant lipid metabolism in mice.

Automated summary

Elemicin exposure can lead to hepatomegaly and mild hepatosteatosis, and depletion of gut microbiota can alleviate this liver damage. Elemicin can also alter the structure of fecal microbiota and affect gut microbiota function. In addition, specific microbial genera are associated with Elemicin exposure and significantly correlated with liver-related indicators such as ALT, AST, and TG.