Affiliation:
1. V. Almazov National Medical Research Center
2. V. Almazov National Medical Research Center; First St. Petersburg State I. Pavlov Medical University
3. Institute of Experimental Medicine
4. First St. Petersburg State I. Pavlov Medical University
5. Moscow Physico-Technical Institute
6. Institute of Experimental Medicine; St. Petersburg State University
Abstract
Experimental medicine provides the scientific community with a plethora of information on therapeutic efficacy of probiotic strains. However, from the point of view of evidence-based medicine, the list of disorders controlled by probiotics is limited to antibiotic-associated diarrhea in adults and children, Clostridium difficile-associated diarrhea, acute infectious diarrhea in children and adults, eradication therapy, ulcerative colitis and irritable bowel syndrome. Recently, these indications are also amended by well-validated clinical guidelines for the usage of probiotic preparations, in order to modulate immunity. Given the permeability of gastrointestinal and immune system barriers for pathogenic and opportunistic microbiota, it seems logical to assume the effectiveness of probiotics as potential symbiotic regulators of nervous and cardiovascular systems. It should also be taken into account that metabolic disorders, e.g., obesity, with a low-intensity inflammatory response and characteristic cytokine pattern, are acquired as a gain of human civilization. In this regard, we propose a scientific hypothesis about the effectiveness of probiotic microbial strains in increasing myocardial resistance to ischemic-reperfusion injury, due to their ability to block individual links of the cytokine cascade during the development of inflammatory response, for its subsequent translation into clinical practice.The development and validation of a new experimental model of systemic inflammatory response syndrome (SIRS) in male Wistar rats, including obesity, acute inflammatory process of the colon, and antibiotic-induced dysbiosis, became basic to the study of efficacy of probiotic drugs in terms of myocardial resistance to ischemicreperfusion injury (IRI). Rats with SIRS showed a significantly increased size of the infarction area (+28%) upon experiments with isolated perfused heart under global ischemia-reperfusion conditions. Significant changes in the leukocyte formula and immunological parameters associated with SIRS were corrected by introduction of a mixture of probiotic strains L. acidophilus (LA-5) and B. animalis subsp. lactis (BB-12), and the isolated strain L. delbrueckii TS1-06. In both groups with probiotic correction, there was a decrease in the infarction area compared to the SIRS group. General and specific changes in IL-2, transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNFa) were noted. The reduction of myocardial infarction by probiotics may be related to the blocking of first-order cytokines, which leads to a «break» of proinflammatory cascade. A need for in-depth study of cardioprotective mechanisms mediated by probiotics was confirmed due to their potential usage as a symbiotic alternative to biological drugs which block the main pro-inflammatory cytokines.
Reference15 articles.
1. Бorschev Yu.Yu., Burovenko I.Yu., Karaseva A.B., Minasyan S.M., Borschev V.Yu., Semenova N.Yu., Borshcheva O.V., Polovinkin V.V., Rodionov G.G., Suvorov A.N., Galagudza M.M. Modeling of systemic inflammatory response syndrome by chemical induction of colon injury in rats. Meditsinskaya immunologiya = Medical Immunology (Russia), 2020, Vol. 22, no. 1, pp. 87-98. (In Russ.) doi: 10.15789/1563-0625MOS-1839.
2. Tretyakova Yu.I., Antipova A.A., Shulkina S.G. Features of the cytokine profile in patients with ulcerative colitis. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education, 2017, no. 6. [Electronic resource]. Access mode: https:// science-education.ru/ru/article/view?id=27276. (In Russ.)]
3. Khavkin A.I., Komarova O.N. Products of Metabolism of the Intestinal Microflora: Can We Use the Selective Correction? Voprosy sovremennoy pediatrii = Current Pediatrics, 2015, Vol. 14, no. 2, pp. 212-218. (In Russ.)
4. Bailey M.T., Coe C.L. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol., 1999, Vol. 35, pp. 146-155.
5. Belizário J.E., Faintuch J., Garay-Malpartida M. Gut microbiome dysbiosis and immunometabolism: new frontiers for treatment of metabolic diseases. Mediators Inflamm., 2018, Vol. 2018, 2037838. doi: 10.1155/2018/2037838.