In summary, our study identified the metagenomic changes around glycan, SCFA, TMA, and amino acid metabolism in primary hypertension patients with antihypertension medications, especially enhanced glycan biosynthesis ability; verified several of SCFA, TMA precursors, and amino acid changes in fecal and plasma samples by LC-MS; and uncovered the potential influence of macrophage-AMPK on these metagenomic changes (Figure 6). This evidence concerns the gene PRKAA1 and essential hypertension.