We identified regulatory networks among genomic variants (GGA6: 5.59–5.69 Mb), gene expression (PEMT and TOM1L2), protein presence (PEMT), and metabolite abundance (SAMe, SAH, PC, PE, and Hcy) in hepatic steatosis and proposed for the first time that duodenal microbiota (m2 = 0.26) played more important roles in hepatic steatosis than other gut segments, and genus Lactobacillus in the duodenum might perform compensatory roles in alleviating hepatic steatosis by production of extra folate to prompt the host methionine cycle. This evidence concerns the gene PEMT and fatty liver disease.