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T-2 toxin causes decreased intestinal colonization of Salmonella Typhimurium in pigs associated with altered gene expression

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Abstract
T-2 toxin is a very stable mycotoxin produced by Fusarium spp. which often ends up in the food and feed chain. It poses a threat to human and animal health, especially to pigs which appear to be one of the most sensitive species (1). It is known that moderate to high levels of T-2 toxin cause feed refusal, vomiting, weight loss, reduced growth and immunosuppression in pigs, which results in considerable economic losses. Besides mycotoxins, Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) infections are a major issue in swine production. Pigs infected with Salmonella Typhimurium can carry this bacterium in their tonsils, gut and gut-associated lymphoid tissue for weeks or even months (2, 3). These carrier pigs excrete very low numbers of Salmonella and are difficult to distinguish from uninfected pigs. However, at slaughter they can be a source of environmental and carcass contamination (4). Several studies describe an altered susceptibility to intestinal infections after ingestion of certain mycotoxins, but until now there are no data available describing a possible interaction between T-2 toxin and the pathogenesis of a Salmonella Typhimurium infection in pigs (5-8). Therefore, the aim of the presented study was to investigate the effects of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. We conducted an in vivo trial in which 3-week-old Salmonella-free piglets were randomized into three groups of 5 piglets and they received, during 23 days, ad libitum blank feed (control group), feed contaminated with 10 µg/kg T-2 toxin (10 ppb group) or feed contaminated with 100 µg/kg T-2 toxin (100 ppb group), respectively. The pigs were orally inoculated with 2 x 107 colony-forming units (CFU) of Salmonella Typhimurium strain 112910a phage type 120/ad. Five days after inoculation, the pigs were humanely euthanized and samples of intestinal contents and tissues were taken for bacteriological analysis. The 10 ppb and 100 ppb group showed reduced numbers of Salmonella Typhimurium in jejunum, cecum (p < 0.05) and colon tissue, and cecum (p < 0.05) and colon contents. These results showed that the presence of low and in practice relevant concentrations of T-2 toxin in the feed reduced the colonization of Salmonella Typhimurium in the intestine. In addition to this, we conducted a microarray analysis to investigate the effect of T-2 toxin on the gene expression of Salmonella Typhimurium. This showed that T-2 toxin, at a concentration as low as 5 ng/ml, has negative effects on the motility (flgL, flgM en flgK) of Salmonella Typhimurium and that it causes a general downregulation of the metabolism of Salmonella Typhimurium in vitro. In conclusion, T-2 toxin severely affects gene expression of Salmonella Typhimurium and causes a reduced colonization of the bacteria in pigs. However, further research is required to determine the effects of these low and in practice relevant concentrations on the gut health of pigs. References: [1] Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001 Oct 15;167(2):101-34 [2] Wood RL, Pospischil A, Rose R. Distribution of persistent Salmonella typhimurium infection in internal organs of swine. Am J Vet Res. 1989 Jul;50(7):1015-21 [3] Boyen F, Haesebrouck F, Maes D, Van Immerseel F, Ducatelle R, Pasmans F. Non-typhoidal Salmonella infections in pigs: a closer look at epidemiology, pathogenesis and control. Vet Microbiol. 2008 Jul 27;130(1-2):1-19 [4] Wong DMALF, Hald T, van der Wolf PJ, Swanenburg M. Epidemiology and control measures for Salmonella in pigs and pork. Livestock Production Science. 2002 Sep;76(3):215-22 [5] Fukata T, Sasai K, Baba E, Arakawa A. Effect of ochratoxin A on Salmonella typhimurium-challenged layer chickens. Avian Dis. 1996 Oct-Dec;40(4):924-6 [6] Oswald IP, Desautels C, Laffitte J, Fournout S, Peres SY, Odin M, et al. Mycotoxin fumonisin B1 increases intestinal colonization by pathogenic Escherichia coli in pigs. Appl Environ Microbiol. 2003 Oct;69(10):5870-4 [7] Stoev SD, Goundasheva D, Mirtcheva T, Mantle PG. Susceptibility to secondary bacterial infections in growing pigs as an early response in ochratoxicosis. Exp Toxicol Pathol. 2000 Aug;52(4):287-96 [8] Tai JH, Pestka JJ. Impaired murine resistance to Salmonella typhimurium following oral exposure to the trichothecene T-2 toxin. Food Chem Toxicol. 1988 Aug;26(8):691-8

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Chicago
Verbrugghe, Elin, Virginie Vandenbroucke, Siska Croubels, Mia Eeckhout, Sarah De Saeger, Joline Goossens, Patrick De Backer, et al. 2011. “T-2 Toxin Causes Decreased Intestinal Colonization of Salmonella Typhimurium in Pigs Associated with Altered Gene Expression.” In Mycotoxins, 4th International Symposium, Abstracts.
APA
Verbrugghe, E., Vandenbroucke, V., Croubels, S., Eeckhout, M., De Saeger, S., Goossens, J., De Backer, P., et al. (2011). T-2 toxin causes decreased intestinal colonization of Salmonella Typhimurium in pigs associated with altered gene expression. Mycotoxins, 4th International symposium, Abstracts. Presented at the 4th International symposium on Mycotoxins (MYTOX 2011) : Challenges and perspectives.
Vancouver
1.
Verbrugghe E, Vandenbroucke V, Croubels S, Eeckhout M, De Saeger S, Goossens J, et al. T-2 toxin causes decreased intestinal colonization of Salmonella Typhimurium in pigs associated with altered gene expression. Mycotoxins, 4th International symposium, Abstracts. 2011.
MLA
Verbrugghe, Elin, Virginie Vandenbroucke, Siska Croubels, et al. “T-2 Toxin Causes Decreased Intestinal Colonization of Salmonella Typhimurium in Pigs Associated with Altered Gene Expression.” Mycotoxins, 4th International Symposium, Abstracts. 2011. Print.
@inproceedings{1245082,
  abstract     = {T-2 toxin is a very stable mycotoxin produced by Fusarium spp. which often ends up in the food and feed chain. It poses a threat to human and animal health, especially to pigs which appear to be one of the most sensitive species (1). It is known that moderate to high levels of T-2 toxin cause feed refusal, vomiting, weight loss, reduced growth and immunosuppression in pigs, which results in considerable economic losses. 
Besides mycotoxins, Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) infections are a major issue in swine production. Pigs infected with Salmonella Typhimurium can carry this bacterium in their tonsils, gut and gut-associated lymphoid tissue for weeks or even months (2, 3). These carrier pigs excrete very low numbers of Salmonella and are difficult to distinguish from uninfected pigs. However, at slaughter they can be a source of environmental and carcass contamination (4). Several studies describe an altered susceptibility to intestinal infections after ingestion of certain mycotoxins, but until now there are no data available describing a possible interaction between T-2 toxin and the pathogenesis of a Salmonella Typhimurium infection in pigs (5-8). Therefore, the aim of the presented study was to investigate the effects of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. 
We conducted an in vivo trial in which 3-week-old Salmonella-free piglets were randomized into three groups of 5 piglets and they received, during 23 days, ad libitum blank feed (control group), feed contaminated with 10 µg/kg T-2 toxin (10 ppb group) or feed contaminated with 100 µg/kg T-2 toxin (100 ppb group), respectively. The pigs were orally inoculated with 2 x 107 colony-forming units (CFU) of Salmonella Typhimurium strain 112910a phage type 120/ad. Five days after inoculation, the pigs were humanely euthanized and samples of intestinal contents and tissues were taken for bacteriological analysis. The 10 ppb and 100 ppb group showed reduced numbers of Salmonella Typhimurium in jejunum, cecum (p < 0.05) and colon tissue, and cecum (p < 0.05) and colon contents. These results showed that the presence of low and in practice relevant concentrations of T-2 toxin in the feed reduced the colonization of Salmonella Typhimurium in the intestine. 
In addition to this, we conducted a microarray analysis to investigate the effect of T-2 toxin on the gene expression of Salmonella Typhimurium. This showed that T-2 toxin, at a concentration as low as 5 ng/ml, has negative effects on the motility (flgL, flgM en flgK) of Salmonella Typhimurium and that it causes a general downregulation of the metabolism of Salmonella Typhimurium in vitro. 
In conclusion, T-2 toxin severely affects gene expression of Salmonella Typhimurium and causes a reduced colonization of the bacteria in pigs. However, further research is required to determine the effects of these low and in practice relevant concentrations on the gut health of pigs. 
References:
[1] Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001 Oct 15;167(2):101-34
[2] Wood RL, Pospischil A, Rose R. Distribution of persistent Salmonella typhimurium infection in internal organs of swine. Am J Vet Res. 1989 Jul;50(7):1015-21
[3] Boyen F, Haesebrouck F, Maes D, Van Immerseel F, Ducatelle R, Pasmans F. Non-typhoidal Salmonella infections in pigs: a closer look at epidemiology, pathogenesis and control. Vet Microbiol. 2008 Jul 27;130(1-2):1-19
[4] Wong DMALF, Hald T, van der Wolf PJ, Swanenburg M. Epidemiology and control measures for Salmonella in pigs and pork. Livestock Production Science. 2002 Sep;76(3):215-22
[5] Fukata T, Sasai K, Baba E, Arakawa A. Effect of ochratoxin A on Salmonella typhimurium-challenged layer chickens. Avian Dis. 1996 Oct-Dec;40(4):924-6
[6] Oswald IP, Desautels C, Laffitte J, Fournout S, Peres SY, Odin M, et al. Mycotoxin fumonisin B1 increases intestinal colonization by pathogenic Escherichia coli in pigs. Appl Environ Microbiol. 2003 Oct;69(10):5870-4
[7] Stoev SD, Goundasheva D, Mirtcheva T, Mantle PG. Susceptibility to secondary bacterial infections in growing pigs as an early response in ochratoxicosis. Exp Toxicol Pathol. 2000 Aug;52(4):287-96
[8] Tai JH, Pestka JJ. Impaired murine resistance to Salmonella typhimurium following oral exposure to the trichothecene T-2 toxin. Food Chem Toxicol. 1988 Aug;26(8):691-8},
  author       = {Verbrugghe, Elin and Vandenbroucke, Virginie and Croubels, Siska and Eeckhout, Mia and De Saeger, Sarah and Goossens, Joline and De Backer, Patrick and Thompson, Arthur and Shearer, Neil and Leyman, Bregje and Van Parys, Alexander and Boyen, Filip and Haesebrouck, Freddy and Pasmans, Frank},
  booktitle    = {Mycotoxins, 4th International symposium, Abstracts},
  language     = {eng},
  location     = {Ghent, Belgium},
  title        = {T-2 toxin causes decreased intestinal colonization of Salmonella Typhimurium in pigs associated with altered gene expression},
  year         = {2011},
}