#14-077

Complete

Date Full Report Received

11/02/2015

Date Abstract Report Received

11/02/2015

Investigation

Institution: , , ,
Primary Investigator:

The gut of pigs can be colonized with important foodborne and disease causing bacteria such as Salmonella, E. coli and Campylobacter. New treatments and strategies are sought to reduce the carriage of these bacteria particularly as they are shipped to the processing plant. Thymol is an attractive candidate to be developed into an antibiotic alternative for swine because it is a natural product and thus likely to be viewed more favorably by regulatory agencies. Thymol is known to exhibit potent antimicrobial activity against Salmonella, E. coli and Campylobacter in the laboratory but its effectiveness when fed to animals is not very good. This is because thymol is very rapidly absorbed in the stomach and small intestine which consequently prevents it from arriving to the cecum and large intestine where these pathogenic bacteria primarily reside. In order to make thymol more resistant to absorption, we chemically linked thymol to glucose using a chemical bond like that used by plants to link glucose units into cellulose. The result is that the conjugated form of thymol, referred to as thymol-beta-D-glucopyranoside (which we will hereafter call beta-D-thymol for ease of use), is absorbed much more slowly than free thymol and thus has the potential to bypass absorption in the stomach and small intestine and make its way to the cecum and large intestine. Conceptually, once the beta-D-thymol arrives to the cecum and intestine, there are gut bacteria there that can degrade the protective bond and thus liberate free thymol, thereby making it available to kill Salmonella, E. coli and Campylobacter. The main objective of this project was to determine if beta-D-thymol could indeed be fed to pigs to reduce gut concentrations of Salmonella, E. coli and Campylobacter. Results from live animal studies were not successful in achieving significant reductions in cecal and rectal concentrations of Salmonella, E. coli or Campylobacter, possibly because hydrolysis and absorption of beta-D-thymol and free thymol may still have been rapid enough within the proximal small intestine to preclude their delivery to the cecum and large intestine. Additionally, it is possible also that uptake and internal compartmentalization of beta-D-thymol by gut bacteria, or its powerful chemical attraction to fats and oils, may sequester the beta-D-thymol away from hydrolytic enzymes thus preventing the release of free thymol. Comparison of antimicrobial resistance profiles between E. coli isolates or multidrug resistant Salmonella strains did not support a hypothesis that exposure to beta-D-thymol or thymol may co-select for antimicrobial resistance. Additional research is currently underway to try and learn how to overcome obstacles preventing efficacious activity of beta-D-thymol to the lower gastrointestinal tract.