Metabolomics Reveals Gut Microbiota Contribute to PPARα Deficiency-Induced Alcoholic Liver Injury

Abstract

Incidence and mortality rates of alcoholic liver disease (ALD) is one of the highest in the world. In the present study, we found that the genetic knockout nuclear receptor the peroxisome proliferator-activated receptor α (PPARα) exacerbated ALD. Lipidomics of the liver revealed changed levels of lipid species encompassing phospholipids, ceramides (CM), and long-chain fatty acids in Ppara-null mice induced by ethanol. Moreover, 4-hydroxyphenylacetic acid (4-HPA) was changed as induced by ethanol in the metabolome of urine. Moreover, the phylum level analysis showed a decrease in the level of Bacteroidetes and an increase in the level of Firmicutes after alcohol feeding in Ppara-null mice, while there was no change in wild-type mice. In Ppara-null mice, the level of Clostridium_sensu_stricto_1 and Romboutsia were upregulated after alcohol feeding. These data revealed that PPARα deficiency potentiated alcohol-induced liver injury through promotion of lipid accumulation, changing the metabolome of urine, and increasing the level of Clostridium_sensu_stricto_1 and Romboutsia. 4-HPA could improve ALD in mice by regulating inflammation and lipid metabolism. Therefore, our findings suggest a novel approach to the treatment of ALD: focusing on the gut microbiota and its metabolites. Data are available via ProteomeXchange (PXD 041465).

Gut microbiota and serum metabolome reveal the mechanism by which TCM polysaccharides alleviate salpingitis in laying hens challenged by bacteria

“…Growing evidence showed that an increased abundance of Romboutsia was associated with inflammatory diseases. Clostridium_sensu_stricto _1 and Romboutsia were significantly upregulated in alcohol-induced liver injury in mice ( Zhang et al, 2023 ), as well as in mice with dextran sulfate-induced colitis. The abundance of Romboutsia was also increased after cephalosporin treatment ( Wang et al, 2022 ).…”

Chlorantraniliprole exposure aggravates high-fat diet-induced metabolic disorders in mice by regulating gut microbiota and its metabolites

“…Apart from changes in amino acid metabolites, the effect of pesticide treatment on OEA, was also observed. Previous studies have indicated that excessive fat intake leads to a reduction in OEA levels in rodents, while OEA supplementation has shown anti-obesity effects [44,45] . Acting as a PPARα agonist, OEA stimulates lipolysis by activating PPARα [46] .…”