Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction

<b>Background/Objectives:</b> <i>Campylobacter jejuni</i> (CJ) is the etiological agent of the world’s most common intestinal infectious food-borne disease, ranging from mild symptoms to fatal outcomes. The development of innovative synbiotics that inhibit the adhesion and re...

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Main Authors: Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Evgenia I. Deryusheva, Tatiana V. Priputnevich, Alexander N. Panin, Irina O. Chikileva, Tatiana N. Abashina, Ashot M. Manoyan, Olga E. Ivanova, Tigran T. Papazyan, Ilia N. Nikonov, Nataliya E. Suzina, Vyacheslav G. Melnikov, Valentin S. Khlebnikov, Vadim K. Sakulin, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh, Vladimir N. Uversky, Andrey V. Karlyshev
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Language:English
Published: MDPI AG 2024-11-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/13/12/1143
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author Vyacheslav M. Abramov
Igor V. Kosarev
Andrey V. Machulin
Evgenia I. Deryusheva
Tatiana V. Priputnevich
Alexander N. Panin
Irina O. Chikileva
Tatiana N. Abashina
Ashot M. Manoyan
Olga E. Ivanova
Tigran T. Papazyan
Ilia N. Nikonov
Nataliya E. Suzina
Vyacheslav G. Melnikov
Valentin S. Khlebnikov
Vadim K. Sakulin
Vladimir A. Samoilenko
Alexey B. Gordeev
Gennady T. Sukhikh
Vladimir N. Uversky
Andrey V. Karlyshev
author_facet Vyacheslav M. Abramov
Igor V. Kosarev
Andrey V. Machulin
Evgenia I. Deryusheva
Tatiana V. Priputnevich
Alexander N. Panin
Irina O. Chikileva
Tatiana N. Abashina
Ashot M. Manoyan
Olga E. Ivanova
Tigran T. Papazyan
Ilia N. Nikonov
Nataliya E. Suzina
Vyacheslav G. Melnikov
Valentin S. Khlebnikov
Vadim K. Sakulin
Vladimir A. Samoilenko
Alexey B. Gordeev
Gennady T. Sukhikh
Vladimir N. Uversky
Andrey V. Karlyshev
author_sort Vyacheslav M. Abramov
collection DOAJ
description <b>Background/Objectives:</b> <i>Campylobacter jejuni</i> (CJ) is the etiological agent of the world’s most common intestinal infectious food-borne disease, ranging from mild symptoms to fatal outcomes. The development of innovative synbiotics that inhibit the adhesion and reproduction of multidrug-resistant (MDR) CJ in animals and humans, thereby preserving intestinal homeostasis, is relevant. We have created a synbiotic based on the consortium of <i>Lactobacillus crispatus</i> 2029 (LC2029), <i>Ligilactobacillus salivarius</i> 7247 (LS7247), and a mannan-rich prebiotic (Actigen<sup>®</sup>). The purpose of this work was to study the in vitro anti-adhesive and antagonistic activities of the created synbiotic against MDR CJ strains, along with its role in preventing intestinal barrier dysfunction, which disrupts intestinal homeostasis. <b>Methods:</b> A complex of microbiological, immunological, and molecular biological methods was used. The ability of the LC2029 and LS7247 consortium to promote intestinal homeostasis in vitro was assessed by the effectiveness of controlling CJ-induced TLR4 activation, secretion of pro-inflammatory cytokines, development of intestinal barrier dysfunction, and production of intestinal alkaline phosphatase (IAP). <b>Results:</b> All MDR CJ strains showed marked adhesion to human Caco-2, pig IPEC-J2, chicken CPCE, and bovine BPCE enterocytes. For the first time, we found that the prebiotic and cell-free culture supernatant (CFS) from the consortium of LC2029 and LS7247 strains exhibit an additive effect in inhibiting the adhesion of MDR strains of CJ to human and animal enterocytes. CFS from the LC2029 and LS7247 consortium increased the permeability of the outer and inner membranes of CJ cells, which led to extracellular leakage of ATP and provided access to the peptidoglycan of the pathogen for the peptidoglycan-degrading bacteriocins nisin and enterolysin A produced by LS7247. The LC2029 and LS7247 consortium showed a bactericidal effect on CJ strains. Co-cultivation of the consortium with CJ strains resulted in a decrease in the viability of the pathogen by 6 log. CFS from the LC2029 and LS7247 consortium prevented the growth of CJ-induced TLR4 mRNA expression in enterocytes. The LC2029 and LS7247 consortium inhibited a CJ-induced increase in IL-8 and TNF-α production in enterocytes, prevented CJ-induced intestinal barrier dysfunction, maintained the transepithelial electrical resistance of the enterocyte monolayers, and prevented an increase in intestinal paracellular permeability and zonulin secretion. CFS from the consortium stimulated IAP mRNA expression in enterocytes. The LC2029 and LS7247 consortium and the prebiotic Actigen represent a new synergistic synbiotic with anti-CJ properties that prevents intestinal barrier dysfunction and preserves intestinal homeostasis. <b>Conclusions:</b> These data highlight the potential of using a synergistic synbiotic as a preventive strategy for creating feed additives and functional nutrition products based on it to combat the prevalence of campylobacteriosis caused by MDR strains in animals and humans.
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spelling doaj-art-9b80ccfbce654217a9a0989a7c1325bc2025-08-20T02:01:05ZengMDPI AGAntibiotics2079-63822024-11-011312114310.3390/antibiotics13121143Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier DysfunctionVyacheslav M. Abramov0Igor V. Kosarev1Andrey V. Machulin2Evgenia I. Deryusheva3Tatiana V. Priputnevich4Alexander N. Panin5Irina O. Chikileva6Tatiana N. Abashina7Ashot M. Manoyan8Olga E. Ivanova9Tigran T. Papazyan10Ilia N. Nikonov11Nataliya E. Suzina12Vyacheslav G. Melnikov13Valentin S. Khlebnikov14Vadim K. Sakulin15Vladimir A. Samoilenko16Alexey B. Gordeev17Gennady T. Sukhikh18Vladimir N. Uversky19Andrey V. Karlyshev20Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, RussiaFederal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, RussiaSkryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, RussiaInstitute for Biological Instrumentation, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, RussiaKulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, RussiaFederal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, RussiaBlokhin National Research Center of Oncology, Ministry of Health, 115478 Moscow, RussiaSkryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, RussiaFederal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, RussiaFederal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, RussiaAlltech Company, 105062 Moscow, RussiaFederal State Budgetary Educational Institution of Higher Education, St. Petersburg State University of Veterinary Medicine, 196084 Saint Petersburg, RussiaSkryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, RussiaGabrichevsky Research Institute for Epidemiology and Microbiology, 125212 Moscow, RussiaInstitute of Immunological Engineering, 142380 Lyubuchany, RussiaInstitute of Immunological Engineering, 142380 Lyubuchany, RussiaSkryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, RussiaKulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, RussiaKulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, RussiaDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Biomolecular Sciences, School of Life Sciences, Chemistry and Pharmacy, Faculty of Health, Science, Social Care and Education, Kingston University London, Kingston upon Thames KT1 2EE, UK<b>Background/Objectives:</b> <i>Campylobacter jejuni</i> (CJ) is the etiological agent of the world’s most common intestinal infectious food-borne disease, ranging from mild symptoms to fatal outcomes. The development of innovative synbiotics that inhibit the adhesion and reproduction of multidrug-resistant (MDR) CJ in animals and humans, thereby preserving intestinal homeostasis, is relevant. We have created a synbiotic based on the consortium of <i>Lactobacillus crispatus</i> 2029 (LC2029), <i>Ligilactobacillus salivarius</i> 7247 (LS7247), and a mannan-rich prebiotic (Actigen<sup>®</sup>). The purpose of this work was to study the in vitro anti-adhesive and antagonistic activities of the created synbiotic against MDR CJ strains, along with its role in preventing intestinal barrier dysfunction, which disrupts intestinal homeostasis. <b>Methods:</b> A complex of microbiological, immunological, and molecular biological methods was used. The ability of the LC2029 and LS7247 consortium to promote intestinal homeostasis in vitro was assessed by the effectiveness of controlling CJ-induced TLR4 activation, secretion of pro-inflammatory cytokines, development of intestinal barrier dysfunction, and production of intestinal alkaline phosphatase (IAP). <b>Results:</b> All MDR CJ strains showed marked adhesion to human Caco-2, pig IPEC-J2, chicken CPCE, and bovine BPCE enterocytes. For the first time, we found that the prebiotic and cell-free culture supernatant (CFS) from the consortium of LC2029 and LS7247 strains exhibit an additive effect in inhibiting the adhesion of MDR strains of CJ to human and animal enterocytes. CFS from the LC2029 and LS7247 consortium increased the permeability of the outer and inner membranes of CJ cells, which led to extracellular leakage of ATP and provided access to the peptidoglycan of the pathogen for the peptidoglycan-degrading bacteriocins nisin and enterolysin A produced by LS7247. The LC2029 and LS7247 consortium showed a bactericidal effect on CJ strains. Co-cultivation of the consortium with CJ strains resulted in a decrease in the viability of the pathogen by 6 log. CFS from the LC2029 and LS7247 consortium prevented the growth of CJ-induced TLR4 mRNA expression in enterocytes. The LC2029 and LS7247 consortium inhibited a CJ-induced increase in IL-8 and TNF-α production in enterocytes, prevented CJ-induced intestinal barrier dysfunction, maintained the transepithelial electrical resistance of the enterocyte monolayers, and prevented an increase in intestinal paracellular permeability and zonulin secretion. CFS from the consortium stimulated IAP mRNA expression in enterocytes. The LC2029 and LS7247 consortium and the prebiotic Actigen represent a new synergistic synbiotic with anti-CJ properties that prevents intestinal barrier dysfunction and preserves intestinal homeostasis. <b>Conclusions:</b> These data highlight the potential of using a synergistic synbiotic as a preventive strategy for creating feed additives and functional nutrition products based on it to combat the prevalence of campylobacteriosis caused by MDR strains in animals and humans.https://www.mdpi.com/2079-6382/13/12/1143<i>Campylobacter</i>multidrug resistancesynbioticsbactericidal activityintestinal homeostasis
spellingShingle Vyacheslav M. Abramov
Igor V. Kosarev
Andrey V. Machulin
Evgenia I. Deryusheva
Tatiana V. Priputnevich
Alexander N. Panin
Irina O. Chikileva
Tatiana N. Abashina
Ashot M. Manoyan
Olga E. Ivanova
Tigran T. Papazyan
Ilia N. Nikonov
Nataliya E. Suzina
Vyacheslav G. Melnikov
Valentin S. Khlebnikov
Vadim K. Sakulin
Vladimir A. Samoilenko
Alexey B. Gordeev
Gennady T. Sukhikh
Vladimir N. Uversky
Andrey V. Karlyshev
Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
Antibiotics
<i>Campylobacter</i>
multidrug resistance
synbiotics
bactericidal activity
intestinal homeostasis
title Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
title_full Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
title_fullStr Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
title_full_unstemmed Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
title_short Consortium of <i>Lactobacillus crispatus</i> 2029 and <i>Ligilactobacillus salivarius</i> 7247 Strains Shows In Vitro Bactericidal Effect on <i>Campylobacter jejuni</i> and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction
title_sort consortium of i lactobacillus crispatus i 2029 and i ligilactobacillus salivarius i 7247 strains shows in vitro bactericidal effect on i campylobacter jejuni i and in combination with prebiotic protects against intestinal barrier dysfunction
topic <i>Campylobacter</i>
multidrug resistance
synbiotics
bactericidal activity
intestinal homeostasis
url https://www.mdpi.com/2079-6382/13/12/1143
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