Multiomic exploration reveals the alterations and connections among gut microbiome, metabolome and transcriptome in obesity

Differences and associations among gut microbiota and metabolites, plasma and liver metabolites, and colonic and liver gene expression in obesity remain unclear. Eight-week-old C57BL/6J mice were fed with high-fat diet for 14 weeks and body weight (BW) were recorded. Colonic content and tissues, plasma, and liver were collected for multi-omics. BW significantly increased from day 21. Firmicutes, Mucispirillum, Lactococcus, Anaerotruncus, deoxyribonucleotides and amino acid biosynthesis were abundant in obesity, whereas Bacteroidetes, Alistipes, Lactobacillus, Muribaculum, Bacteroides and saccharides degradation were reduced. Colonic transcriptomics revealed the upregulated genes in obesity were mainly focused on cholesterol metabolism, tryptophan metabolism, PPAR signaling pathway, lipid metabolism, transport and localization. Colonic metabolomics verified decreased oxidized lipids while increased amino acids, coEnzyme and and vitamins, nucleotides, organic acids in obesity. In liver, the highly expressed genes were mainly involved in MAPK signaling pathway, PPAR signaling pathway, neurotransmitter transport, fatty acid biosynthesis and metabolism in obesity. Liver metabolomics further revealed oxidized lipids, organic acids, nucleotides, coEnzyme and vitamines, and amino acids were enriched in obesity. We systematically demonstrated changes and relationships among gut microbiota, colonic, plasma and liver metabolites, colonic and liver gene expression, providing new evidence for comprehensive understanding of obesity.