Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis

Background Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection. Methods We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection. Results Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection. Conclusions This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection

Persistent changes in spinal cord gene expression after recovery from inflammatory hyperalgesia: A preliminary study on pain memory

<p>Abstract</p> <p>Background</p> <p>Previous studies found that rats subjected to carrageenan injection develop hyperalgesia, and despite complete recovery in several days, they continue to have an enhanced hyperalgesic response to a new noxious challenge for more than 28d. The study's aim was to identify candidate genes that have a role in the formation of the long-term hyperalgesia-related imprint in the spinal cord. This objective was undertaken with the understanding that the long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity.</p> <p>Results</p> <p>To analyze changes in gene expression when carrageenan-induced hyperalgesia has disappeared but propensity for the enhanced hyperalgesic response is still present, we determined the gene expression profile using oligo microarray in the lumbar part of the spinal cord in three groups of rats: 28d after carrageenan injection, 24h after injection (the peak of inflammation), and with no injection (control group). Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01). Among differentially expressed genes, 67 (39 in 28d group) were identified as being part of pain-related pathways, altered in different models of pain, or interacting with proteins involved in pain-related pathways. Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.</p> <p>Conclusion</p> <p>Despite recovery from inflammatory hyperalgesia, persistent changes in spinal cord gene expression may underlie the propensity for the enhanced hyperalgesic response. We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.</p

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

Comparative Effects of Sandalwood Seed Oil on Fatty Acid Profiles and Inflammatory Factors in Rats

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague–Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n-3 polyunsaturated fatty acids (PUFA) levels but lower n-6:n-3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n-3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n-3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F2α, prostaglandin E2, thromboxane B2, leukotriene B4, tumor necrosis factor-α and interleukin-1β in both liver and plasma were positively correlated with the n-6:n-3 ratios, suggesting that increased n-6 PUFA appear to increase the formation of pro-inflammatory cytokines, whereas n-3 PUFA exhibit anti-inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n-3 PUFA, DHA and reduce the n-6:n-3 ratio, and may increase the anti-inflammatory activity in rats