Effect of pro- and metabiotic Lactobacillus delbrueckii D5 strain on myocardial resistance to ischemia – reperfusion injury in the rat model of systemic inflammatory response

Aim. To study the effect of lyophilized L. delbrueckii D5, as well as its inactivated culture, during intragastric administration on myocardial resistance to ischemia – reperfusion injury (IRI), markers of inflammation, and intestinal epithelial permeability.
Materials and methods. The experiments were performed on male Wistar rats with a model of systemic inflammatory response syndrome (SIRS). Myocardial IRI was reproduced on an isolated Langendorff heart.
Results. A significant increase in the levels of tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, and lactoferrin in SIRS was revealed. The introduction of both inactivated and lyophilized culture of L. delbrueckii D5 resulted in normalization of these changes. Normalization of the increased blood level of lipopolysaccharide in SIRS was also noted with the introduction of both inactivated and lyophilized L. delbrueckii D5. However, the inactivated culture had no effect on the myocardial infarct size, which was increased in the SIRS group compared to the controls, whereas the introduction of the lyophilized strain led to a significant decrease in this parameter.
Conclusion. The inactivated culture of Lactobacillus delbrueckii D5 has a pronounced anti-inflammatory effect, but does not impact myocardial resistance to IRI, unlike the lyophilized strain, which requires further research.

1. Zhang Y., Wang Y., Ke B., Du J. TMAO: how gut microbiota contributes to heart failure. Transl. Res. 2021;228:109–125. DOI: 10.1016/j.trsl.2020.08.007.

2. Борщев Ю.Ю., Буровенко И.Ю., Карасева А.Б., Минасян С.М., Борщев В.Ю., Семенова Н.Ю. и др. Моделирование синдрома системной воспалительной реакции химической индукцией травмы толстого кишечника у крыс. Медицинская иммунология. 2020;22(1):87–98. DOI: 10.15789/1563-0625-MOS-1839.

3. Borshchev Y.Y., Burovenko I.Y., Karaseva A.B., Minasian S.M., Protsak E.S., Borshchev V.Y. et al. Probiotic therapy with Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis results in infarct size limitation in rats with obesity and chemically induced colitis. Microorganisms. 2022;10(11):2293. DOI: 10.3390/microorganisms10112293.

4. Карасёва А.Б., Буровенко И.Ю., Цапиева А.Н., Борщев Ю.Ю., Суворов А.Н., Галагудза М.М. Изменения состава кишечной микробиоты при моделировании системного воспалительного ответа у крыс разного возраста. Университетский терапевтический вестник. 2022;4(2):42–51. DOI: 10.56871/4633.2022.37.29.005.

5. Олескин А.В., Шендеров Б.А. Пробиотики, психобиотики и метабиотики: проблемы и перспективы. Физическая и реабилитационная медицина, медицинская реабилитация. 2020;2(3):233–243. DOI: 10.36425/rehab25811.

6. Минасян С.М., Бадриханова Л.Р., Галагудза М.М., Курапеев Д.И. Сравнительное исследование защитного эффекта гипотермии, ишемического прекондиционирования и модифицированных кардиоплегических растворов при ишемии-реперфузии изолированного сердца крысы. Регионарное кровообращение и микроциркуляция. 2008;2(26):72–78.

7. Di Vincenzo F., Del Gaudio A., Petito V., Lopetuso L.R., Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern. Emerg. Med. 2024;19(2):275–293. DOI: 10.1007/s11739-023-03374-w.

8. Ghosh S., Ahmad R., Zeyaullah M., Khare S.K. Microbial nano-factories: synthesis and biomedical applications. Front. Chem. 2021;9:626834. DOI: 10.3389/fchem.2021.626834.

9. Peng L., Li Z.R., Green R.S., Holzman I.R., Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 2009;139(9):161901625. DOI: 10.3945/jn.109.104638.

10. Cario E., Gerken G., Podolsky D.K. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology. 2004;127(1):224–238. DOI: 10.1053/j.gastro.2004.04.015.

11. Yi H., Wang L., Xiong Y., Wang Z., Qiu Y., Wen X. et al. Lactobacillus reuteri LR1 improved expression of genes of tight junction proteins via the MLCK pathway in IPEC1 cells during infection with enterotoxigenic Escherichia coli K88. Mediators Inflamm. 2018;2018:6434910. DOI: 10.1155/2018/6434910.

12. Zhao L., Xie Q., Etareri Evivie S., Liu D., Dong J., Ping L. et al. Bifidobacterium dentium N8 with potential probiotic characteristics prevents LPS-induced intestinal barrier injury by alleviating the inflammatory response and regulating the tight junction in Caco-2 cell monolayers. Food Funct. 2021;12(16):7171–7184. DOI: 10.1039/D1FO01164B

13. Hsieh C.Y., Osaka T., Moriyama E., Date Y., Kikuchi J., Tsuneda S. Strengthening of the intestinal epithelial tight junction by Bifidobacterium bifidum. Physiol. Rep. 2015;3(3):e12327. DOI: 10.14814/phy2.12327.

14. Zhao X., Zhou J., Liang W., Sheng Q., Lu L., Chen T. et al. Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway. Cell Biosci. 2021;11(1):20. DOI: 10.1186/s13578-021-00530-7.

15. Blackwood B.P., Yuan C.Y., Wood D.R., Nicolas J.D., Grothaus J.S., Hunter C.J. Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. J. Probiotics Health. 2017;5(1):159. DOI: 10.4172/2329-8901.1000159.

16. Francavilla R., Miniello V., Magistà A.M., De Canio A., Bucci N., Gagliardi F. et al. A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain. Pediatrics. 2010;126(6):e1445–1452. DOI: 10.1542/peds.2010-0467.

17. Mujagic Z., de Vos P., Boekschoten M.V., Govers C., Pieters H.H., de Wit N.J. et al. The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial. Sci. Rep. 2017;7:40128. DOI: 10.1038/srep40128.

18. Zheng Y., Zhang Z., Tang P., Wu Y., Zhang A., Li D. et al. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front. Immunol. 2023;14:1143548. DOI: 10.3389/fimmu.2023.1143548.

19. Cheng F.S., Pan D., Chang B., Jiang M., Sang L.X. Probiotic mixture VSL#3: An overview of basic and clinical studies in chronic diseases. World J. Clin. Cases. 2020;8(8):1361–1384. DOI: 10.12998/wjcc.v8.i8.1361.