Lawsonia intracellularis is among the most important enteric pathogens of swine and antibiotic alternatives are needed to help mitigate the negative effects of infection. Zinc is an essential trace mineral known to be crucial for maintaining intestinal barrier function and proper immune response. In this study, we investigated the porcine host response to L. intracellularis infection when supplemented with a zinc-amino acid complex, a form of zinc that can lead to greater bioavailability when compared to traditional inorganic forms of zinc. Our results show that a zinc-amino acid complex supplementation with a final concentration of 125 ppm of zinc in feed significantly (p < 0.05) decreased the number of animals with lesions and severity of lesions caused by L. intracellularis. Animals supplemented with the zinc-amino acid complex also exhibited a significantly (p < 0.05) earlier onset of seroconversion as well as an increased number of T cells in infected and non-infected intestinal tissue. This study demonstrated that this zinc-amino acid complex aids the host in responding to L. intracellularis infection and may be a new approach to help minimize negative effects of disease.
Background Serotonin (5‐hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity. Objective To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity. Animals Fourteen healthy Beagle dogs were used in this study. Methods Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF‐5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system. Results Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, P = .025). Adiponectin and 5‐hydroytryptamine of cerebrospinal fluid ( CSF ‐5 HT ) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, P = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group. Conclusions and Clinical Importance Decreased 5 HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram‐negative might be related with chronic inflammation status in obese dogs.
The effects of three bacterial pathogens on the villus architecture of small intestines and the role that bacterial virulence factors play in pathogenesis are described. Bacterial pathogens cause a spectrum of effects ranging from severe tissue damage to a lack of perceptible damage. Enterotoxigenic Escherichia coli, which cause acute and severe diarrhea, does so by producing potent toxins, but these toxins act by altering the biological activity in epithelial cells. However, the cells are not damaged. Enteropathogenic E. coli and Salmonella, on the other hand cause various degrees of tissue damage. As part of their pathogenesis, they employ a type III protein secretion system to orchestrate internal changes in target cells. The expression of many virulence related genes is tightly regulated and appears to be turned on in response to cues found in the intestinal tract. The consequences of this level of regulation also is discussed.
Lawsonia intracellularis causes porcine proliferative enteropathy. This is an enteric disease characterized by thickening of the wall of the ileum that leads to decreased growth of animals and diarrhea. In this study, we investigated the host response to L. intracellularis infection by performing transcriptomic and pathway analysis of intestinal tissue samples from groups of infected and noninfected animals at 14, 21, and 28 days postchallenge. At the peak of infection, when animals developed the most severe lesions, infected animals had higher levels of several gene transcripts involved in cellular proliferation and inflammation, including matrix metalloproteinase-7 (MMP7), transglutaminase-2 (TGM2), and oncostatin M (OSM). Histomorphology also revealed general features of intestinal inflammation. This study identified important pathways associated with the host response in developing and resolving lesions due to L. intracellularis infection.IMPORTANCELawsonia intracellularis is among the most important enteric pathogens of swine, and it can also infect other mammalian species. Much is still unknown regarding its pathogenesis and the host response, especially at the site of infection. In this study, we uncovered several novel genes and pathways associated with infection. Differentially expressed transcripts, in addition to histological changes in infected tissue, revealed striking similarities between L. intracellularis infection and cellular proliferation mechanisms described in some cancers and inflammatory diseases of the gastrointestinal tract. This research sheds important light into the pathogenesis of L. intracellularis and the host response associated with the lesions caused by infection.
Research in my laboratory has been on the mechanism(s) employed by Salmonella typhimurium to persistently colonize pigs and on the factors contributing to increased shedding of S. typhimurium by pigs at slaughter. A phenotype of S. typhimurium has been identified that attaches to epithelial cells isolated from the pig small intestine. Cells of the adhesive phenotype produce pili that may be the adhesin, while cells of the non-adhesive phenotype do not. Cells of the adhesive phenotype also produce 10-12 unique envelope proteins and several new surface antigens. Adhesive cells are more readily phagocytized by porcine neutrophils and macrophages and have a much greater degree of intracellular survival in the phagocytic cells. Cells can readily shift between the two phenotypes. In the laboratory the rate of change is between 10-2 and 10-4. When pigs were challenged with cells in the nonadhesive phenotype, only cells in the adhesive phenotype were recovered from pigs. Both phenotypes were of equal virulence. This demonstrates that the adhesive phenotype is important in pigs. A nonadhesive mutant was isolated and shown to be less virulent in mice and was more rapidly cleared from the intestinal tract of pigs. The role of the adhesin and the other properties associated with the adhesive phenotype are being investigated with the intent of learning how pigs can be long term carriers of S. typhimurium.
Salmonella enterica serovar Typhimurium strain 798 has previously been shown to undergo phenotypic phase variation. One of the phenotypes expresses virulence traits such as adhesion, while the other phenotype does not. Phenotypic phase variation appears to correlate with the ability of this strain to cause persistent, asymptomatic infections of swine. A new method to detect cells in either phenotypic phase was developed using Evans Blue-Uranine agar plates. Using this new assay, rates of phenotypic phase variation were obtained. The rate of phase variation from non-adhesive to adhesive phenotype was approximately 10−4 per cell per generation while phase variation from the adhesive to the non-adhesive phenotype was approximately 10−6 per cell per generation. Two highly virulent S. Typhimurium strains, SL1344 and ATCC 14028, were also shown to undergo phase variation. However, while the rate from adhesive to non-adhesive phenotype was approximately the same as for strain 798, the non-adhesive to adhesive phenotype shift was 37-fold higher. Differential gene expression was measured using RNA-Seq. Eighty-three genes were more highly expressed by 798 cells in the adhesive phenotype compared to the non-adhesive cells. Most of the up-regulated genes were in virulence genes and in particular all genes in the Salmonella pathogenicity island 1 were up-regulated. When compared to the virulent strain SL1344, expression of the virulence genes was approximately equal to those up-regulated in the adhesive phenotype of strain 798. A comparison of invasive ability demonstrated that strain SL1344 was the most invasive followed by the adhesive phenotype of strain 798, then the non-adhesive phenotype of strain 798. The least invasive strain was ATCC 14028. The genome of strain 798 was sequenced and compared to SL1344. Both strains had very similar genome sequences and gene deletions could not readily explain differences in the rates of phase variation from non-adhesive to the adhesive phenotype.
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