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Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs

Levent, Gizem; Anderson, Robin C.; Petrujkić, Branko; Poole, Toni L.; He, Haiqi; Genovese, Kenneth J.; Hume, Michael E.; Beier, Ross C.; Harvey, Roger B.; Nisbet, David J.

(MDPI, 2021)

TY  - JOUR
AU  - Levent, Gizem
AU  - Anderson, Robin C.
AU  - Petrujkić, Branko
AU  - Poole, Toni L.
AU  - He, Haiqi
AU  - Genovese, Kenneth J.
AU  - Hume, Michael E.
AU  - Beier, Ross C.
AU  - Harvey, Roger B.
AU  - Nisbet, David J.
PY  - 2021
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2221
AB  - The gut of food-producing animals is a reservoir for foodborne pathogens. Thymol is bactericidal against foodborne pathogens but rapid absorption of thymol from the proximal gut precludes the delivery of effective concentrations to the lower gut where pathogens mainly colonize. Thymol-β-d-glucopyranoside is reported to be more resistant to absorption than thymol in everted jejunal segments and could potentially function as a prebiotic by resisting degradation and absorption in the proximal gut but being hydrolysable by microbial β-glycosidase in the distal gut. Previous in vitro studies showed bactericidal effects of thymol-β-d-glucopyranoside against Campylobacter, Escherichia coli, and Salmonella enterica serovar Typhimurium in the presence but not absence of intestinal microbes expressing β-glycosidase activity, indicating that hydrolysis was required to obtain antimicrobial activity. Presently, the oral administration of thymol-β-d-glucopyranoside was studied to examine the effects on intestinal carriage of Campylobacter, E. coli, and S. Typhimurium in swine. The effects of thymol-β-d-glucopyranoside or thymol on antimicrobial sensitivity of representative E. coli isolates and characterized Salmonella strains were also explored. Results from two in vivo studies revealed little antimicrobial effects of thymol-β-d-glucopyranoside on Campylobacter, E. coli, or S. Typhimurium in swine gut. These findings add credence to current thinking that hydrolysis and absorption of thymol-β-d-glucopyranoside and thymol may be sufficiently rapid within the proximal gut to preclude delivery to the distal gut. Antibiotic susceptibilities of selected bacterial isolates and strains were mainly unaffected by thymol. Further research is warranted to overcome obstacles, preventing the delivery of efficacious amounts of thymol-β-d-glucopyranoside to the lower gut.
PB  - MDPI
T2  - Microorganisms
T1  - Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs
VL  - 9
IS  - 4
SP  - 860
DO  - 10.3390/microorganisms9040860
ER  - 
@article{
author = "Levent, Gizem and Anderson, Robin C. and Petrujkić, Branko and Poole, Toni L. and He, Haiqi and Genovese, Kenneth J. and Hume, Michael E. and Beier, Ross C. and Harvey, Roger B. and Nisbet, David J.",
year = "2021",
abstract = "The gut of food-producing animals is a reservoir for foodborne pathogens. Thymol is bactericidal against foodborne pathogens but rapid absorption of thymol from the proximal gut precludes the delivery of effective concentrations to the lower gut where pathogens mainly colonize. Thymol-β-d-glucopyranoside is reported to be more resistant to absorption than thymol in everted jejunal segments and could potentially function as a prebiotic by resisting degradation and absorption in the proximal gut but being hydrolysable by microbial β-glycosidase in the distal gut. Previous in vitro studies showed bactericidal effects of thymol-β-d-glucopyranoside against Campylobacter, Escherichia coli, and Salmonella enterica serovar Typhimurium in the presence but not absence of intestinal microbes expressing β-glycosidase activity, indicating that hydrolysis was required to obtain antimicrobial activity. Presently, the oral administration of thymol-β-d-glucopyranoside was studied to examine the effects on intestinal carriage of Campylobacter, E. coli, and S. Typhimurium in swine. The effects of thymol-β-d-glucopyranoside or thymol on antimicrobial sensitivity of representative E. coli isolates and characterized Salmonella strains were also explored. Results from two in vivo studies revealed little antimicrobial effects of thymol-β-d-glucopyranoside on Campylobacter, E. coli, or S. Typhimurium in swine gut. These findings add credence to current thinking that hydrolysis and absorption of thymol-β-d-glucopyranoside and thymol may be sufficiently rapid within the proximal gut to preclude delivery to the distal gut. Antibiotic susceptibilities of selected bacterial isolates and strains were mainly unaffected by thymol. Further research is warranted to overcome obstacles, preventing the delivery of efficacious amounts of thymol-β-d-glucopyranoside to the lower gut.",
publisher = "MDPI",
journal = "Microorganisms",
title = "Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs",
volume = "9",
number = "4",
pages = "860",
doi = "10.3390/microorganisms9040860"
}
Levent, G., Anderson, R. C., Petrujkić, B., Poole, T. L., He, H., Genovese, K. J., Hume, M. E., Beier, R. C., Harvey, R. B.,& Nisbet, D. J.. (2021). Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs. in Microorganisms
MDPI., 9(4), 860.
https://doi.org/10.3390/microorganisms9040860
Levent G, Anderson RC, Petrujkić B, Poole TL, He H, Genovese KJ, Hume ME, Beier RC, Harvey RB, Nisbet DJ. Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs. in Microorganisms. 2021;9(4):860.
doi:10.3390/microorganisms9040860 .
Levent, Gizem, Anderson, Robin C., Petrujkić, Branko, Poole, Toni L., He, Haiqi, Genovese, Kenneth J., Hume, Michael E., Beier, Ross C., Harvey, Roger B., Nisbet, David J., "Evaluation of Thymol-β-d-Glucopyranoside as a Potential Prebiotic Intervention to Reduce Carriage of Zoonotic Pathogens in Weaned and Feeder Pigs" in Microorganisms, 9, no. 4 (2021):860,
https://doi.org/10.3390/microorganisms9040860 . .
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Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro

Anderson, Robin C.; Levent, Gizem; Petrujkić, Branko; Harvey, Roger B.; Hume, Michael E.; He, Haiqi; Genovese, Kenneth J.; Beier, Ross C.; Poole, Toni L.; Crippen, Tawni L.; Nisbet, David J.

(Frontiers Media, 2021)

TY  - JOUR
AU  - Anderson, Robin C.
AU  - Levent, Gizem
AU  - Petrujkić, Branko
AU  - Harvey, Roger B.
AU  - Hume, Michael E.
AU  - He, Haiqi
AU  - Genovese, Kenneth J.
AU  - Beier, Ross C.
AU  - Poole, Toni L.
AU  - Crippen, Tawni L.
AU  - Nisbet, David J.
PY  - 2021
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2224
AB  - Strategies are sought to reduce the carriage and dissemination of zoonotic pathogens and antimicrobial-resistant microbes within food-producing animals and their production environment. Thymol (an essential oil) is a potent bactericide in vitro but in vivo efficacy has been inconsistent, largely due to its lipophilicity and absorption, which limits its passage and subsequent availability in the distal gastrointestinal tract. Conjugation of thymol to glucose to form thymol-β-d-glucopyranoside can decrease its absorption, but in vivo passage of effective concentrations to the lower gut remains suboptimal. Considering that contemporary swine diets often contain 5% or more added fat (to increase caloric density and reduce dustiness), we hypothesized that there may be sufficient residual fat in the distal intestinal tract to sequester free or conjugated thymol, thereby limiting the availability and subsequent effectiveness of this biocide. In support of this hypothesis, the anti-Salmonella Typhimurium effects of 6 mM free or conjugated thymol, expressed as log10-fold reductions of colony-forming units (CFU) ml−1, were diminished 90 and 58%, respectively, following 24-h in vitro anaerobic fecal incubation (at 39°C) with 3% added vegetable oil compared to reductions achieved during culture without added oil (6.1 log10 CFU ml−1). The antagonistic effect of vegetable oil and the bactericidal effect of free and conjugated thymol against Escherichia coli K88 tested similarly were diminished 86 and 84%, respectively, compared to reductions achieved in cultures incubated without added vegetable oil (5.7 log10 CFU ml−1). Inclusion of taurine (8 mg/ml), bile acids (0.6 mg/ml), or emulsifiers such as polyoxyethylene-40 stearate (0.2%), Tween 20, or Tween 80 (each at 1%) in the in vitro incubations had little effect on vegetable oil-caused inhibition of free or conjugated thymol. Based on these results, it seems reasonable to suspect that undigested lipid in the distal gut may limit the effectiveness of free or conjugated thymol. Accordingly, additional research is warranted to learn how to overcome obstacles diminishing bactericidal activity of free and conjugated thymol in the lower gastrointestinal tract of food-producing animals.
PB  - Frontiers Media
T2  - Frontiers in Veterinary Science
T1  - Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro
VL  - 8
SP  - 1053
DO  - 10.3389/fvets.2021.751266
ER  - 
@article{
author = "Anderson, Robin C. and Levent, Gizem and Petrujkić, Branko and Harvey, Roger B. and Hume, Michael E. and He, Haiqi and Genovese, Kenneth J. and Beier, Ross C. and Poole, Toni L. and Crippen, Tawni L. and Nisbet, David J.",
year = "2021",
abstract = "Strategies are sought to reduce the carriage and dissemination of zoonotic pathogens and antimicrobial-resistant microbes within food-producing animals and their production environment. Thymol (an essential oil) is a potent bactericide in vitro but in vivo efficacy has been inconsistent, largely due to its lipophilicity and absorption, which limits its passage and subsequent availability in the distal gastrointestinal tract. Conjugation of thymol to glucose to form thymol-β-d-glucopyranoside can decrease its absorption, but in vivo passage of effective concentrations to the lower gut remains suboptimal. Considering that contemporary swine diets often contain 5% or more added fat (to increase caloric density and reduce dustiness), we hypothesized that there may be sufficient residual fat in the distal intestinal tract to sequester free or conjugated thymol, thereby limiting the availability and subsequent effectiveness of this biocide. In support of this hypothesis, the anti-Salmonella Typhimurium effects of 6 mM free or conjugated thymol, expressed as log10-fold reductions of colony-forming units (CFU) ml−1, were diminished 90 and 58%, respectively, following 24-h in vitro anaerobic fecal incubation (at 39°C) with 3% added vegetable oil compared to reductions achieved during culture without added oil (6.1 log10 CFU ml−1). The antagonistic effect of vegetable oil and the bactericidal effect of free and conjugated thymol against Escherichia coli K88 tested similarly were diminished 86 and 84%, respectively, compared to reductions achieved in cultures incubated without added vegetable oil (5.7 log10 CFU ml−1). Inclusion of taurine (8 mg/ml), bile acids (0.6 mg/ml), or emulsifiers such as polyoxyethylene-40 stearate (0.2%), Tween 20, or Tween 80 (each at 1%) in the in vitro incubations had little effect on vegetable oil-caused inhibition of free or conjugated thymol. Based on these results, it seems reasonable to suspect that undigested lipid in the distal gut may limit the effectiveness of free or conjugated thymol. Accordingly, additional research is warranted to learn how to overcome obstacles diminishing bactericidal activity of free and conjugated thymol in the lower gastrointestinal tract of food-producing animals.",
publisher = "Frontiers Media",
journal = "Frontiers in Veterinary Science",
title = "Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro",
volume = "8",
pages = "1053",
doi = "10.3389/fvets.2021.751266"
}
Anderson, R. C., Levent, G., Petrujkić, B., Harvey, R. B., Hume, M. E., He, H., Genovese, K. J., Beier, R. C., Poole, T. L., Crippen, T. L.,& Nisbet, D. J.. (2021). Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro. in Frontiers in Veterinary Science
Frontiers Media., 8, 1053.
https://doi.org/10.3389/fvets.2021.751266
Anderson RC, Levent G, Petrujkić B, Harvey RB, Hume ME, He H, Genovese KJ, Beier RC, Poole TL, Crippen TL, Nisbet DJ. Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro. in Frontiers in Veterinary Science. 2021;8:1053.
doi:10.3389/fvets.2021.751266 .
Anderson, Robin C., Levent, Gizem, Petrujkić, Branko, Harvey, Roger B., Hume, Michael E., He, Haiqi, Genovese, Kenneth J., Beier, Ross C., Poole, Toni L., Crippen, Tawni L., Nisbet, David J., "Antagonistic Effects of Lipids Against the Anti-Escherichia coli and Anti-Salmonella Activity of Thymol and Thymol-β-d-Glucopyranoside in Porcine Gut and Fecal Cultures In Vitro" in Frontiers in Veterinary Science, 8 (2021):1053,
https://doi.org/10.3389/fvets.2021.751266 . .
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