Metabolomics profiling in acute liver transplant rejection in a pediatric population.

Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p < 0.05) showed bile acid biosynthesis and tryptophan metabolism as the top two differentiating pathways. Network analysis also identified tryptophan and clustered with liver enzymes and steroid use. We conclude metabolic profiling of plasma from children with acute liver transplant rejection demonstrates > 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.

Iron Fortification and Supplementation: Fighting Anemia of Chronic Diseases or Fueling Obesity?

The significant worldwide increase in obesity has become a major health problem. Excess adiposity has been extensively linked to inflammation. Recently, studies have shown that dietary intake and microbiota dysbiosis can affect the health of the gut and lead to low-grade systemic inflammation, worsening the state of obesity and further exacerbating inflammation. The latter is shown to decrease iron status and potentially increase the risk of anemia by inhibiting iron absorption. Hence, anemia of obesity is independent of iron intake and does not properly respond to increased iron ingestion. Therefore, countries with a high rate of obesity should assess the health impact of fortification and supplementation with iron due to their potential drawbacks. This review tries to elucidate the relation between inflammation and iron status to better understand the etiology of anemia of obesity and chronic diseases and wisely design any dietary or medical interventions for the management of anemia and/or obesity.