Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats

BACKGROUND:Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS:We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE:These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases

A systematic review of the effect of nutrition, diet and dietary change on learning, behaviour and performance of school-aged children

Lower blood folate levels have been associated with depression in several cross-sectional surveys, but longitudinal studies are needed to assess whether depression is a consequence or a cause of folate deficiency.The Southampton Women’s Survey (SWS) comprises a cohort of 12 500 non-pregnant women recruited from the general population between 1998 and 2002 who are being followed through subsequent pregnancies. The SWS has been shown to be broadly representative of the general population1. From March 2000 all 7210 women recruited into the study were asked to complete a GHQ12 questionnaire to assess depression and anxiety2. All women were asked to provide venous blood samples from which erythrocyte folate (RCF) was assayed using an Abbott microparticle enzyme immunoassay IMx-folate kit and an IMx analyzer. Consent was obtained from the women to access their general practitioner (GP) records to obtain evidence of incident depression over the 2-year period following the baseline interview. Complete GHQ12 data were provided by 7020 women (97%) and RCF measurements were obtained for 5051 (72%) of them. Among the 5051 women 1588 (31%) were identified as depressed at the baseline survey. Using Poisson regression modelling with RCF as a continuous variable it was found that RCF was inversely associated with the risk of depression. The prevalence ratio associated with an increase in RCF of 100 nmol/l was 0.985 (95% CI 0.974, 0.995; P=0.005); those with RCF levels <960 nmol/l were 14% more likely to be depressed than those with higher levels. The association was attenuated after adjustment for confounding factors (P=0.05) but still indicated that lower RCF levels were linked to depression (prevalence ratio 0.98 (95% CI 0.97, 1.00; P=0.05). Follow-up data were available for 3996 women whose RCF levels had been measured (79%). The 1264 women who were identified as depressed at baseline either from the GP notes or from the GHQ12 questionnaire were excluded. Of the remaining 2732 women 307 (11%) had an incident episode of depression recorded by their GP in the 2 years following baseline interview. In a Cox regression model no relationship between RCF and incident depression was identified; the unadjusted hazard ratio per 100 nmol/l increase in RCF was 0.99 (95% CI 0.96, 1.02; P=0.4) and the adjusted hazard ratio was 1.00 (95% CI 0.97, 1.03; P=0.9). The finding of an association between RCF and prevalence of depression in a cross-sectional analysis but not with incident depression during follow-up of the cohort indicates that lower RCF levels may be more a consequence than a cause of depression. However, a positive association with incident depression cannot be excluded as smaller numbers of women contributed to the follow-up than to the cross-sectional analysis. Nonetheless, the 95% CI associated with the hazard ratio indicates that even a 100 nmol/l increase in RCF would be unlikely to reduce the risk of depression by more than about 3%. Thus, the contribution of low folate status to depression appears modest, and folate supplementation to prevent depression does not seem warranted on the basis of these findings