Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity

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Abstract

Obesity is associated with changes in the gut microbiota, as well as 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 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, TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota.

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About the authors

I. M. Kolesnikova

N.I. Pirogov Russian National Research Medical University; The National Medical Research Center for Endocrinology

Author for correspondence.
Email: ir.max.kolesnikova@gmail.com
Russian Federation, Moscow, 117997; Moscow, 117292

L. A. Ganenko

Rostov State Medical University

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Rostov-on-Don, 344002

I. Yu. Vasilyev

Kazan (Volga region) Federal University

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Kazan, 420008

T. V. Grigoryeva

Kazan (Volga region) Federal University

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Kazan, 420008

N. I. Volkova

Rostov State Medical University

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Rostov-on-Don, 344002

S. A. Roumiantsev

N.I. Pirogov Russian National Research Medical University; The National Medical Research Center for Endocrinology; Center for Molecular Health

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Moscow, 117997; Moscow, 117292; Moscow, 117437

A. V. Shestopalov

N.I. Pirogov Russian National Research Medical University; The National Medical Research Center for Endocrinology; Center for Molecular Health; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: ir.max.kolesnikova@gmail.com
Russian Federation, Moscow, 117997; Moscow, 117292; Moscow, 117437; Moscow, 117997

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Supplementary files

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2. Fig. 1. Analysis of the concentration of trefoil factors in the blood serum (a) and the metabolic profile of the intestinal microbiota (b) in patients with MHO and MNHO. Here and below: H is the value of the Kruskal-Wallis H-test, p is the significance level of the Kruskal-Wallis H-test. Horizontal bars show the differences between the groups revealed using the post-hoc test according to the Conover method (p < 0.05).

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3. Fig. 2. Analysis of energy metabolism pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO. From here on: graphs are constructed based on the medians of the corresponding metabolic processes; error bars represent the 25th and 75th percentiles. TCA cycle – tricarboxylic acid cycle; CoA – coenzyme A. From here on: vertical bars show the differences between the groups identified using the post-hoc test according to Conover’s method (p < 0.05).

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4. Fig. 3. Analysis of water-soluble vitamin synthesis pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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5. Fig. 4. Analysis of terpene and quinone biosynthetic pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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6. Fig. 5. Analysis of nucleotide metabolic pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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7. Fig. 6. Analysis of nucleic acid processing pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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8. Fig. 7. Analysis of iron and heme metabolism pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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9. Fig. 8. Analysis of amino acid metabolism pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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10. Fig. 9. Analysis of the prevalence of aromatic compound degradation pathways in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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11. Fig. 10. Analysis of the pathways for the synthesis of structural components in the metabolic profiles of the microbiome of patients with MHO and MNHO.

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