Abstract
Cases of unpredictable, idiosyncratic liver damage of moxifloxacin (MXF) have been occasionally reported. However, the health effects of MXF exposure remain controversial. The current study examined the metabolic phenotypes and intestinal flora characteristics of hepatotoxicity induced by MXF. Rats were administered moxifloxacin hydrochloride tablets at doses of 36, 72, and 108 mg/kg body weight/day for 21 days. The levels of tricarboxylic acid cycle intermediates were decreased, whereas those of lipids (arachidonic acid, hexadecanoic acid, and linoleic acid) were increased, reflecting disorders of energy-related and lipid metabolism. Enrichment analysis of the differential metabolites suggested that butanoate metabolism was associated with MXF-induced liver injury. 16S rRNA sequencing uncovered that the diversity of gut intestinal was decreased in MXF-treated rats. Specifically, the abundance of Muribaculaceae was increased, whereas that of Lachnospiraceae, a family of butyrate-producing bacteria, was decreased. The combined serum metabonomics and gut microbiome datasets illustrated the involvement of butanoic acid and energy metabolism in the regulatory changes of the gut-liver axis associated with MXF-induced liver injury. The regulation of endogenous small molecules and intestinal flora during drug-induced liver injury was first described from the perspective of the gut-liver axis, providing a research basis for the mechanism of clinical drug-induced liver injury.