As we discussed above, the correlation analysis between differential metabolites and bacteria revealed that active metabolites of Akkermansia and Lactobacillus were closely related to the host inositol phosphate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, which indicated there was a significant crosstalk between the gut microbiota and the host metabolism in ACTH-induced TRD rats. The gene discussed is POMC; the disease is treatment resistant depression.