Multi-omics reveals diet-induced metabolic disorders and liver inflammation via microbiota-gut-liver axis

Abstract

The gut microbiota medicated gut-liver axis is vital for liver function and health. We aimed to explore the underlying molecular mechanism of diet-induced metabolic liver disorders via microbiota-gut-liver axis using multi-omics. Metataxonomics, metaproteomics, transcriptomics, and metabolomics were conducted on liver tissue and biofluids (gastrointestinal contents and blood) to elucidate the microbial mechanism related to metabolic disorders and liver injury. The hepatic inflammation occurred based on histomorphology after feeding a long-term grain-based high-energy diet, and the serum biochemical parameters and proinflammatory cytokines were significantly activated. Metaproteomics analysis indicated that the high-energy diet reduced anti-infection, immunity, anti-oxidant functions, and increased cell death and damage of rumen microbiome. Ruminal Ruminococcus_2, Solobacterium, and Syntrophococcu and jejunal Pirellula were potential microbial markers of liver disorders. The high-energy diet promoted hepatic inflammatory response and cytokine/chemokine-mediated signaling pathways located in the core of the functional genomic network. The high-energy diet increased indoxyl sulfate and p-cresol sulfate and decreased triterpenoids in the liver that were the potential biomarkers associated with metabolic liver disorders. Integrated multi-omics analyses showed interactions among the rumen and jejunum microbiota, circulating metabolites, and liver gene expression, suggesting a systemic immune response and liver disorder that signals through the microbiota-gut-liver axis.

Keywords: Cytokine; Gut-liver axis; Immune response; Liver disorder; Metaproteomics; Rumen microbiome.