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Анотація
Метою дослідження було визначення імуномодулюльної активності ферментолізату пробіотичної культури Lactobacillus delbrueckii subsp. bulgaricus LB86 для розроблення на його основі функціонально активної речовини з цілеспрямованою дією для застосування в косметології та медицині. В експериментах in vitro та in vivo на експериментальній моделі інтактних мишей лінії BALB/c досліджували вплив ферментолізату на функціональну активність макрофагів перитонеального ексудату тварин і продукцію імунорегуляторних цитокінів за допомогою традиційних методів дослідження. Ферментолізат L. delbrueckii subsp. bulgaricus LB86 виявив імуномодулювальну активність, спрямовану на зміну активності макрофагів, а також продукцію про- та протизапальних цитокінів, які беруть участь в імунній відповіді Th1- і Th2-типу. Під дією ферментолізату in vitro спостерігалося підвищення показника фагоцитозу (PhI) макрофагів черевної порожнини інтактних мишей лінії BALB/c. Внутрішньошлункове введення лізату приводило до підвищення у сироватці крові мишей показників спонтанного і стимульованого NBT -тесту макрофагів, збільшення ( на 6 добу після його введення) рівнів IL-12 і IFN-γ та зростання співвідношення INF-γ/IL-4, що вказувало на його потенційну здатність активувати клітинну імунну відповідь. Встановлено, що ферментолізат L. delbrueckii subsp. bulgaricus LB86 після внутрішньошлункового введення інтактним мишам не бере безпосередньої участі в модуляції кишкової мікробіоти. Протягом усього періоду спостереження чисельність аеробних та факультативно анаеробних стафілококів, стрептококів, коліморфних бактерій, лакто- та біфідобактерій, а також мікроскопічних грибів залишалась на рівні контрольних значень. Отримано дані щодо імуномодулювальної активності ферментолізату L. delbrueckii subsp. bulgaricus LB86 можуть вказувати на потенційні перспективи його практичного використання в лікувально-профілактичних засобах.
Ключові слова:
Lactobacillus, ферментолізат, цитокіни, макрофаги, імуномодулювальний ефект
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Як цитувати
LаzarenkoL., OrіabinskaL., & Bohdan, T. (2024). ІМУНОМОДУЛЮВАЛЬНА AКТИВНІСТЬ ФЕРМЕНТОЛІЗАТУ LACTOBACILLUS DELBRUECKII SUBSP. BULGARICUS LB 86. Food Science and Technology, 18(2). https://doi.org/10.15673/fst.v18i2.2903
Номер
Розділ
Біопроцеси, біотехнологія харчових продуктів, БАР
Посилання
1. Zerrin Erginkaya, Gözde Konuray-Altun. Potential biotherapeutic properties of lactic acid bacteria in foods Food Bioscience. [Internet]. 2022 April; 46, 101544. Available from: https:// 10.1016/j.fbio.2022.101544
2. Oyetayo VO, Oyetayo FL. Potential of probiotics as biotherapeutic agents targeting the innate immune system. Afr. J. Biotechnol. 2005; 4 (2): 123-127. Available from: http://www.academicjournals.org/AJB
3. Dzuba О.S, Bohdan T.Z., Orіabinska. L.B., Dugan O.M. Biotherapeutic properties of lactobacilli. Problems of environmental and medical genetics and clinical immunology. 2013; 4(118) :19-29 (in Ukrainian).
4. Julio Plaza-Diaz, Francisco Javier Ruiz-Ojeda, Mercedes Gil-Campos, Angel Gil Mechanisms of Action of Probiotics. Advances in Nutrition (Bethesda, Md.). 2019;10 (1):49–66. Available from: https 10.1093/advances/nmy063
5. Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021. https://doi.org/10.3390/nu9091021
6. Pfefferle P I, Prescott S L, Kopp M. Microbial influence on tolerance and opportunities for intervention with prebiotics/probiotics and bacterial lysates. J. AllergyClin.Immunol. [Internet]. 2013;131(6):14533 Аviable frome: https:// 10.1016/j.jaci.2013.03.020
7. Zhuo Q, Yu B, Zhou J. et al. Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model. Sci Rep 9, [Internet]. 2019; 20128. Available from: https:// 10.1038/s41598-019-56661-y
8. Сrespo C. Bacterial derivatives of Lactococcus lactis and ectoin for atopic dermatitis: dermal compatibility and cosmetic acceptability. Pharm Pharmacol Int J. 2017;5(6):226-231. Available from: https:// 10.15406/ppij.2017.05.00143
9. Mohammedsaeed W, Cruickshank S, McBain AJ, O'Neill CA. Lactobacillus rhamnosus GG fermentolysate increases re-epithelialization of keratinocyte scratch assays by promoting migration. Scientific reports. [Internet]. 2015; 5, 16147. Available from: https:// 10.1038/srep16147
10. Lew L, Liong M. Bioactives from probiotics for dermal health: functions and benefits. J Appl Microbiol. 2013; 114:1241–1253. Available from: https:// 10.1111/jam.12137
11. Sharma D, Kober M M, Bowe W P. Anti-aging effects of probiotics. Journal of drugs in dermatology. 2016; 15(1):9–12.
12. Kim H, Kim HR, Kim NR, Jeong BJ, Lee JS, Jang S, Chung DK. Oral administration of Lactobacillus plantarum lysates attenuates the development of atopic dermatitis lesions in mouse models. J Microbiol. 2015 Jan;53(1):47-52. Available from: https:// 10.1007/s12275-015-4483-z. Epub 2014 Dec 4. PMID: 25471185
13. Ashraf, Rabia, Shah, Nagendra. Immune System Stimulation by Probiotic Microorganisms. Critical reviews in food science and nutrition. 2014; (54). 938–956. Available from: https:// 10.1080/10408398.2011.619671
14. Ding YH, Qian LY, Pang J, Lin J. Y, Xu Q, Wang L.H, Huang D.S, Zou, H. The regulation of immune cells by Lactobacilli: a potential therapeutic target for anti-atherosclerosis therapy. Oncotarget. 2017; 8(35): 59915–59928. Available from: https:// 10.18632/oncotarget.18346
15. Md. Abul Kalam Azad, Manаbendrа Sarker, Dan Wan Immunomodulatory effects of probiotics on cytokine profiles. Biomed Res Int. [Internet]. 2018: 8063647. Available from: https://10.1155/20)18/8063647
16. Teame T, Wang A, Xie M, Zhang Z, Yang Y, Ding Q, Gao C, Olsen RE, Ran C, Zhou Z. Paraprobiotics and Postbiotics of Probiotic Lactobacilli. Their Positive Effects on the Host and Action Mechanisms: A Review. Front Nutr. [Internet]. 2020 Oct 22; 7:570344. Available from: https:// 10.3389/fnut.2020.570344. PMID: 33195367; PMCID: PMC7642493.
17. Thorakkattu P, Khanashyam A C, Shah K, Babu K S, Mundanat A. S, Deliephan A et al. Postbiotics: current trends in food and pharmaceutical industry. Foods. 2022; 1: 3094. Available from: https:// 10.3390/foods11193094
18. Sashihara T, Sueki N, Ikegami S. An analysis of the effectiveness of heat-killed lactic acid bacteria in alleviating allergic diseases. J Dairy Sci. 2006 Aug;89(8):2846-55. Available from: https:// 10.3168/jds.S0022-0302(06)72557-7. PMID: 16840600.
19. Khan MW, Zadeh M, Bere P, Gounaris E, Owen J, Klaenhammer T, Mohamadzadeh M. Modulating intestinal immune responses by lipoteichoic acid-deficient Lactobacillus acidophilus. Immunotherapy. 2012 Feb;4(2):151-61. Available from: https:// 10.2217/imt.11.163. PMID: 22339459; PMCID: PMC3286340.
20. Izuddin WI, Loh TC, Foo HL et al. Postbiotic L. plantarum RG14 improves ruminal epithelium growth, immune status and upregulates the intestinal barrier function in post-weaning lambs. Sci Rep 9. 2019; 9938. Available from: https:// /10.1038/s41598-019-46076-0
21. Zakostelska Z, Kverka M, Klimesova K, Rossmann P, Mrazek J, Kopecny J, Hornova M, Srutkova D, Hudcovic T, Ridl J, Tlaskalova-Hogenova H, Ryffel B. Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PLoS ONE. 2011November; 6:e27961. Available from: https:// 10.1371/journal.pone.0027961
22. Gao K, Wang C, Liu L, Dou X, Liu J, Yuan L, Zhang W, Wang H. Immunomodulation and signaling mechanism of Lactobacillus rhamnosus GG and its components on porcine intestinal epithelial cells stimulated by lipopolysaccharide. J Microbiol Immunol Infect. 2017 Oct; 50(5): 700-713. Available from: https:// 10.1016/j.jmii.2015.05.002. Epub 2015 May 14. PMID: 26055689
23. Yoon K, Lee S, Keum GB, Song K, Park J, Song B, Yu SY, Cho JH, Kim ES, Doo H, Kwak J, Kim S, Eun J, Lee JH, Kim HB, Lee J, Kim J. Characteristics of Lactococcus petauri GB97 lysate isolated from porcine feces and its in vitro and in vivo effects on inflammation, intestinal barrier function, and gut microbiota composition in mice. Microbiol Spectr. 2024; 12:e01334-23. Available from: https:// 10.1128/spectrum.01334-23
24. Coviello S, Wimmenauer V, Polack FP, Irusta PM. Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4. Hum Vaccin Immunother. 2014;10(10):2896-902. Available from: https:// 10.4161/hv.29784. Epub 2014 Nov 19. PMID: 25483455; PMCID: PMC5443103.
25. Probiotics: Biology, Geneticsand Health (Min–Tze Liong – editor) – Malaysia: “Springer Science&Business Media” 2011.
26. Orіabinska LB, Bohdan TZ, Todosiichuk TS. Lactic acid bacteria fermentolysates and their effect on skin hydration. Food Science and Technology. 2021; 15(4): 32-39. Available from: https://10.15673/fst.v15i4.2255
27. Zapadnyuk IP, edition. Laboratory animals: breeding, maintenance, use in experiment. Kyiv: Higher school; 1983 (in Ukrainian).
28. World Gastroenterology Organisation Global Guidelines. Probiotics and prebiotics. 2023 February. Available from: https://www.worldgastroenterology.org/UserFiles/file/guidelines/probiotics-and-prebiotics-english-2023.pdf
29. Lazarenko LM, Babenko LP, Gichka SG, Sakhno LO, Demchenko OM, Bubnov RV, Sichel LM, Spivak MYa. Assessment of the Safety of Lactobacillus casei IMV B-7280 Probiotic Strain on a Mouse Model. Probiotics Antimicrob Proteins. 2021 Dec;13(6):1644-1657. doi: 10.1007/s12602-021-09789-1. Epub 2021 Apr 20. PMID: 33876388; PMCID: PMC8055307.
30. Modzolevsky AF, Dyachenko NS, Spivak N Ya, edition. Modern methods of diagnosis of viral respiratory infections and their therapy using interferon preparations (Methodological recommendations). Кyiv; 1994 (in Ukrainian).
31. Shehadul Islam M, Aryasomayajula A, Selvaganapathy PR. A review on macroscale and microscale cell lysis methods. Micromachines (Basel). 2017 Mar 8;8(3):83. Available from: https:// 10.3390/mi8030083
32. Akulevich OV, Oryabinska L.B, Dugan O.M. Kinetics of growth of lactic acid bacteria of the genus Lactobacillus on nutrient media with various sources of carbon and nitrogen nutrition. KPI Science News. 2013; 3: 7-11. (in Ukrainian).
33. 17.34Yoon-Doo Lee, Yi-Fan Hong, Boram Jeon, Bong Jun Jung, Dae Kyun Chung, and Hangeun Kim Differential cytokine regulatory effect of three Lactobacillus strains isolated from fermented foods. J. Microbiol. Biotechnol. 2016; 26(9):1517–1526. Available from: https://10.4014/jmb.1601.01044
34. 18.35Gad M, Ravn P, Søborg DA, Lund-Jensen K, Ouwehand AC, Jensen S. Regulation of the IL-10/IL-12 axis in human dendritic cells with probiotic bacteria. FEMS Immunol Med Microbiol. Available from: https://10.1111/j.1574-695X.2011.00835.x
2. Oyetayo VO, Oyetayo FL. Potential of probiotics as biotherapeutic agents targeting the innate immune system. Afr. J. Biotechnol. 2005; 4 (2): 123-127. Available from: http://www.academicjournals.org/AJB
3. Dzuba О.S, Bohdan T.Z., Orіabinska. L.B., Dugan O.M. Biotherapeutic properties of lactobacilli. Problems of environmental and medical genetics and clinical immunology. 2013; 4(118) :19-29 (in Ukrainian).
4. Julio Plaza-Diaz, Francisco Javier Ruiz-Ojeda, Mercedes Gil-Campos, Angel Gil Mechanisms of Action of Probiotics. Advances in Nutrition (Bethesda, Md.). 2019;10 (1):49–66. Available from: https 10.1093/advances/nmy063
5. Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021. https://doi.org/10.3390/nu9091021
6. Pfefferle P I, Prescott S L, Kopp M. Microbial influence on tolerance and opportunities for intervention with prebiotics/probiotics and bacterial lysates. J. AllergyClin.Immunol. [Internet]. 2013;131(6):14533 Аviable frome: https:// 10.1016/j.jaci.2013.03.020
7. Zhuo Q, Yu B, Zhou J. et al. Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model. Sci Rep 9, [Internet]. 2019; 20128. Available from: https:// 10.1038/s41598-019-56661-y
8. Сrespo C. Bacterial derivatives of Lactococcus lactis and ectoin for atopic dermatitis: dermal compatibility and cosmetic acceptability. Pharm Pharmacol Int J. 2017;5(6):226-231. Available from: https:// 10.15406/ppij.2017.05.00143
9. Mohammedsaeed W, Cruickshank S, McBain AJ, O'Neill CA. Lactobacillus rhamnosus GG fermentolysate increases re-epithelialization of keratinocyte scratch assays by promoting migration. Scientific reports. [Internet]. 2015; 5, 16147. Available from: https:// 10.1038/srep16147
10. Lew L, Liong M. Bioactives from probiotics for dermal health: functions and benefits. J Appl Microbiol. 2013; 114:1241–1253. Available from: https:// 10.1111/jam.12137
11. Sharma D, Kober M M, Bowe W P. Anti-aging effects of probiotics. Journal of drugs in dermatology. 2016; 15(1):9–12.
12. Kim H, Kim HR, Kim NR, Jeong BJ, Lee JS, Jang S, Chung DK. Oral administration of Lactobacillus plantarum lysates attenuates the development of atopic dermatitis lesions in mouse models. J Microbiol. 2015 Jan;53(1):47-52. Available from: https:// 10.1007/s12275-015-4483-z. Epub 2014 Dec 4. PMID: 25471185
13. Ashraf, Rabia, Shah, Nagendra. Immune System Stimulation by Probiotic Microorganisms. Critical reviews in food science and nutrition. 2014; (54). 938–956. Available from: https:// 10.1080/10408398.2011.619671
14. Ding YH, Qian LY, Pang J, Lin J. Y, Xu Q, Wang L.H, Huang D.S, Zou, H. The regulation of immune cells by Lactobacilli: a potential therapeutic target for anti-atherosclerosis therapy. Oncotarget. 2017; 8(35): 59915–59928. Available from: https:// 10.18632/oncotarget.18346
15. Md. Abul Kalam Azad, Manаbendrа Sarker, Dan Wan Immunomodulatory effects of probiotics on cytokine profiles. Biomed Res Int. [Internet]. 2018: 8063647. Available from: https://10.1155/20)18/8063647
16. Teame T, Wang A, Xie M, Zhang Z, Yang Y, Ding Q, Gao C, Olsen RE, Ran C, Zhou Z. Paraprobiotics and Postbiotics of Probiotic Lactobacilli. Their Positive Effects on the Host and Action Mechanisms: A Review. Front Nutr. [Internet]. 2020 Oct 22; 7:570344. Available from: https:// 10.3389/fnut.2020.570344. PMID: 33195367; PMCID: PMC7642493.
17. Thorakkattu P, Khanashyam A C, Shah K, Babu K S, Mundanat A. S, Deliephan A et al. Postbiotics: current trends in food and pharmaceutical industry. Foods. 2022; 1: 3094. Available from: https:// 10.3390/foods11193094
18. Sashihara T, Sueki N, Ikegami S. An analysis of the effectiveness of heat-killed lactic acid bacteria in alleviating allergic diseases. J Dairy Sci. 2006 Aug;89(8):2846-55. Available from: https:// 10.3168/jds.S0022-0302(06)72557-7. PMID: 16840600.
19. Khan MW, Zadeh M, Bere P, Gounaris E, Owen J, Klaenhammer T, Mohamadzadeh M. Modulating intestinal immune responses by lipoteichoic acid-deficient Lactobacillus acidophilus. Immunotherapy. 2012 Feb;4(2):151-61. Available from: https:// 10.2217/imt.11.163. PMID: 22339459; PMCID: PMC3286340.
20. Izuddin WI, Loh TC, Foo HL et al. Postbiotic L. plantarum RG14 improves ruminal epithelium growth, immune status and upregulates the intestinal barrier function in post-weaning lambs. Sci Rep 9. 2019; 9938. Available from: https:// /10.1038/s41598-019-46076-0
21. Zakostelska Z, Kverka M, Klimesova K, Rossmann P, Mrazek J, Kopecny J, Hornova M, Srutkova D, Hudcovic T, Ridl J, Tlaskalova-Hogenova H, Ryffel B. Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PLoS ONE. 2011November; 6:e27961. Available from: https:// 10.1371/journal.pone.0027961
22. Gao K, Wang C, Liu L, Dou X, Liu J, Yuan L, Zhang W, Wang H. Immunomodulation and signaling mechanism of Lactobacillus rhamnosus GG and its components on porcine intestinal epithelial cells stimulated by lipopolysaccharide. J Microbiol Immunol Infect. 2017 Oct; 50(5): 700-713. Available from: https:// 10.1016/j.jmii.2015.05.002. Epub 2015 May 14. PMID: 26055689
23. Yoon K, Lee S, Keum GB, Song K, Park J, Song B, Yu SY, Cho JH, Kim ES, Doo H, Kwak J, Kim S, Eun J, Lee JH, Kim HB, Lee J, Kim J. Characteristics of Lactococcus petauri GB97 lysate isolated from porcine feces and its in vitro and in vivo effects on inflammation, intestinal barrier function, and gut microbiota composition in mice. Microbiol Spectr. 2024; 12:e01334-23. Available from: https:// 10.1128/spectrum.01334-23
24. Coviello S, Wimmenauer V, Polack FP, Irusta PM. Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4. Hum Vaccin Immunother. 2014;10(10):2896-902. Available from: https:// 10.4161/hv.29784. Epub 2014 Nov 19. PMID: 25483455; PMCID: PMC5443103.
25. Probiotics: Biology, Geneticsand Health (Min–Tze Liong – editor) – Malaysia: “Springer Science&Business Media” 2011.
26. Orіabinska LB, Bohdan TZ, Todosiichuk TS. Lactic acid bacteria fermentolysates and their effect on skin hydration. Food Science and Technology. 2021; 15(4): 32-39. Available from: https://10.15673/fst.v15i4.2255
27. Zapadnyuk IP, edition. Laboratory animals: breeding, maintenance, use in experiment. Kyiv: Higher school; 1983 (in Ukrainian).
28. World Gastroenterology Organisation Global Guidelines. Probiotics and prebiotics. 2023 February. Available from: https://www.worldgastroenterology.org/UserFiles/file/guidelines/probiotics-and-prebiotics-english-2023.pdf
29. Lazarenko LM, Babenko LP, Gichka SG, Sakhno LO, Demchenko OM, Bubnov RV, Sichel LM, Spivak MYa. Assessment of the Safety of Lactobacillus casei IMV B-7280 Probiotic Strain on a Mouse Model. Probiotics Antimicrob Proteins. 2021 Dec;13(6):1644-1657. doi: 10.1007/s12602-021-09789-1. Epub 2021 Apr 20. PMID: 33876388; PMCID: PMC8055307.
30. Modzolevsky AF, Dyachenko NS, Spivak N Ya, edition. Modern methods of diagnosis of viral respiratory infections and their therapy using interferon preparations (Methodological recommendations). Кyiv; 1994 (in Ukrainian).
31. Shehadul Islam M, Aryasomayajula A, Selvaganapathy PR. A review on macroscale and microscale cell lysis methods. Micromachines (Basel). 2017 Mar 8;8(3):83. Available from: https:// 10.3390/mi8030083
32. Akulevich OV, Oryabinska L.B, Dugan O.M. Kinetics of growth of lactic acid bacteria of the genus Lactobacillus on nutrient media with various sources of carbon and nitrogen nutrition. KPI Science News. 2013; 3: 7-11. (in Ukrainian).
33. 17.34Yoon-Doo Lee, Yi-Fan Hong, Boram Jeon, Bong Jun Jung, Dae Kyun Chung, and Hangeun Kim Differential cytokine regulatory effect of three Lactobacillus strains isolated from fermented foods. J. Microbiol. Biotechnol. 2016; 26(9):1517–1526. Available from: https://10.4014/jmb.1601.01044
34. 18.35Gad M, Ravn P, Søborg DA, Lund-Jensen K, Ouwehand AC, Jensen S. Regulation of the IL-10/IL-12 axis in human dendritic cells with probiotic bacteria. FEMS Immunol Med Microbiol. Available from: https://10.1111/j.1574-695X.2011.00835.x