Obesity is associated with changes in the gut microbiota, as well as with increased permeability of the intestinal wall. In 130 non-obese volunteers, 57 patients with metabolically healthy obesity (MHO), and 76 patients with metabolically unhealthy obesity (MUHO), bacterial DNA was isolated from stool samples, and the 16S rRNA gene was sequenced. The metabolic profile of the microbiota predicted by PICRUSt2 (https://huttenhower.sph.harvard.edu/picrust/) was more altered in patients with MUHO than MHO. Obesity, especially MUHO, was accompanied by an increase in the ability of the gut microbiota to degrade energy substrates, produce energy through oxidative phosphorylation, synthesize water-soluble vitamins (B1, B6, B7), nucleotides, heme, aromatic amino acids, and protective structural components of cells. Such changes may be a consequence of the microbiota adaptation to the MUHO-specific conditions. Thus, a vicious circle is formed, when MUHO promotes the depletion of the gut microbiome, and further degeneration of the latter contributes to the pathogenesis of metabolic disorders. The concentration of the trefoil factor family (TFF) in the serum of the participants was also determined. In MHO and MUHO patients, the TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota.