Influence of changes in the human intestinal microbiota on slowing the wound process in overweight persons

Overweight and imbalance of the intestinal microbiota are risk factors for disruption of reparative processes during the healing of postoperative wounds. Given the scale of the obesity epidemic in the modern world, the number of overweight patients undergoing surgery for various reasons is also increasing. Potentiation of the risk of a delayed and complicated course of the wound process with a combination of obesity and disturbances in the composition of the intestinal microbiota determines the relevance of this study.

Purpose of the study: to study the composition of the intestinal microbiota in patients with overweight and obesity, who have a slowdown in the course of the wound process and the development of complications in the postoperative period.

Material and methods. The composition of the intestinal parietal microbiota was studied by microbial markers in the blood using gas chromatography in 49 overweight women who underwent planned surgical interventions for aesthetic indications aimed at correcting body contours from 2019 to 2020. After surgery, women were followed up for 6 months, assessing the timing of wound healing. A comparative analysis of the composition of the intestinal microbiota was carried out in different courses of the wound process, the prognostic significance of individual indicators of the intestinal microbiota was studied in relation to the risk of delayed and complicated wound healing.

Results. In the postoperative period, three groups were formed: 1st − complicated wound process (n = 21), 2nd − slow wound process 16 (n = 16), 3rd − standard wound process (n = 12). There were statistically significant differences between the 1st and 2nd groups in terms of “Peptostreptococcus anaerobius (Gr 1) ≥ 562.0 · 105 cells/g”, p = 0.025) and “Propionibacterium ≥3.2 · 105 cells/g”, p = 0.0136). Differences were found between the 1st and 3rd groups in terms of “Endotoxin ≥0.7 nmol/ml”, p = 0.051). The highest risk of complicated and delayed postoperative wound healing is observed when the value of the indicators «Propionibacterium ≥32.0 · 105 cells/g”, “Peptostreptococcus anaerobius (Gr 1) ≥7.0 · 105 cells/g” and “Endotoxin ≥0.7 nmol/ml”. On the basis of the decision tree method, 4 risk classes of a delayed and complicated course of the wound process were identified. The highest risk is in patients with a combination of factors “Propionibacterium ≥ 3.2 · 105 cells/g” and “Endotoxin ≥ 0.7 nmol/ml”.

Conclusion. A number of indicators of intestinal microbiota have a high prognostic value in relation to the risk of developing a complicated and delayed course of the wound process in overweight individuals. The data obtained can be used to predict unfavorable healing of surgical wounds. 

1. Aitbaev K.A., Murkamilov I.T. Kishechnaya mikrobiota: rol' v patogeneze arterial'noy gipertenzii [Intestinal microbiota: its role in pathogenesis of arterial hypertension]. Klinicheskaya meditsina – Clinical Medicine. 2017;95(2):123-126. (in Russ). DOI: 10.18821/0023-2149-2017-95-2-123-126

2. Artemyeva O.V., Gankovskaya L.V. Vospalitel'noye stareniye kak osnova vozrast-assotsiirovannoy patologii [Inflammaging as the basis of age-associated diseases]. Meditsinskaya Immunologiya – Medical Immunology (Russia). 2020;22(3):419-432 (in Russ). DOI: 10.15789/1563-0625-IAT-1938

3. Sittipo P., Lobionda S., Lee Y.K., Maynard CL. Intestinal microbiota and the immune system in metabolic diseases. J Microbiol. 2018;56(3):154-162. DOI: 10.1007/s12275-018-7548-y

4. Bobunov D.N., Iordanishvili A.K., Mikhailov V.D., Shapurko O.N. Rol' mikrobioty kishechnika v reabilitacii bol'nyh s ozhireniyem [Role of normal intestinal microflora (microbiotas) in rehabilitation of patients with obesity]. Eksperimental'naya i klinicheskaya gastroenterologiya – Experimental and Clinical Gastroenterology. 2019;5:105-110 (in Russ). DOI: 10.31146/1682-8658-ecg-165-5-105-110

5. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019;76(3):473-493. DOI: 10.1007/s00018-018-2943-4

6. Muñoz-Garach A., Diaz-Perdigones C., Tinahones F.J. Gut microbiota and type 2 diabetes mellitus. Endocrinol Nutr. 2016;63(10):560-568. DOI: 10.1016/j.endonu.2016.07.008

7. Pang M., Zhu M., Lei X., Xu P., Cheng B. Microbiome Imbalances: An Overlooked Potential Mechanism in Chronic Nonhealing Wounds. Int J Low Extrem Wounds. 2019;18(1):31-41. DOI: 10.1177/1534734619832754

8. Yudin S.M., Egorova A.M., Makarov V.V. Analiz mikrobioty cheloveka. Rossiyskiy i zarubezhnyy opyt [Analysis of human microbiota. Russian and foreign experience]. Mezhdunarodnyi zhurnal prikladnykh i fundamental'nykh issledovanii. 2018;11-1:175-180. (in Russ).

9. Belenkov Yu.N., Privalova E.V., Kaplunova V.Yu., Zektser V.Yu., Vinogradova N.N., et al. Metabolicheskiy sindrom: istoriya razvitiya, osnovnyye kriterii diagnostiki [Metabolic Syndrome: development of the issue, main diagnostic criteria]. Ratsional'naya farmakoterapiya v kardiologii – Rational Pharmacotherapy in Cardiology. 2018;14(5):757-764 (in Russ). DOI: 10.20996/1819-6446-2018-14-5-757-764

10. Pence B.D., Woods J.A. Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies. Adv Wound Care (New Rochelle). 2014;3(1):71-79. DOI: 10.1089/wound.2012.0377.

11. Olsson M., Järbrink K., Divakar U., Bajpai R., Upton Z., et al.. The humanistic and economic burden of chronic wounds: A systematic review. Wound Repair Regen. 2019;27(1):114-125. DOI: 10.1111/wrr.12683.

12. Grinevich V.B., Radchenko V.G. Mikrobiota kishechnika i metabolicheskiy sindrom [Gut microbiota and metabolic syndrome]. Eksperimental'naya i klinicheskaya gastroenterologiya – Experimental and Clinical Gastroenterology. 2020;183(11):11-19 (In Russ.). DOI: 10.31146/1682-8658-ecg-183-11-11-19

13. Abenavoli L., Scarpellini E., Colica C., Boccuto L., Salehi B., et al. Gut Microbiota and Obesity: A Role for Probiotics. Nutrients. 2019;11(11):2690. DOI: 10.3390/nu11112690

14. Monaghan M., Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol. 2018;36(1):14-20. DOI: 10.1016/j.clindermatol.2017.09.004

15. Pitocco D., Di Leo M., Tartaglione L., De Leva F., Petruzziello C., et al. The role of gut microbiota in mediating obesity and diabetes mellitus. Eur Rev Med Pharmacol Sci. 2020;24(3):1548-1562. DOI: 10.26355/eurrev_202002_20213

16. Le Chatelier E., Nielsen T., Qin J., Prifti E., Hildebrand F., et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541-546. DOI: 10.1038/nature12506

17. Tang W.H.W., Bäckhed F., Landmesser U., Hazen S.L. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(16): 2089-2105. DOI: 10.1016/j.jacc. 2019.03.024

18. Alam A, Neish A. Role of gut microbiota in intestinal wound healing and barrier function. Tissue Barriers. 2018;6(3):1539595. DOI: 10.1080/21688370.2018.1539595

19. Wolcott R., Sanford N., Gabrilska R., Oates J.L., Wilkinson J.E., Rumbaugh K.P. Microbiota is a primary cause of pathogenesis of chronic wounds. J Wound Care. 2016;25 (Sup10):33-43. DOI: 10.12968/jowc.2016.25.Sup10.S33