title: Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis.
abstract: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis may affect multiple organs, including the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality. The underlying mechanisms for sustained inflammation in sarcoidosis are unknown. We hypothesized that metabolic changes play a critical role in perpetuation of inflammation in sarcoidosis.1H nuclear magnetic resonance (NMR)-based untargeted metabolomic analysis was used to identify circulating molecules in serum to discriminate sarcoidosis patients from healthy controls. Principal component analyses (PCA) were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite software, we identified and quantified metabolites responsible for such separation in the PCA models. Quantitative analysis showed that the levels of metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamineN-oxide were significantly increased in sarcoidosis patients. Interestingly, succinate, a major intermediate metabolite involved in the tricyclic acid cycle was significantly decreased in sarcoidosis patients. Application of integrative pathway analyses identified deregulation of butanoate, ketone bodies, citric cycle metabolisms, and transmethylation. This may be used for development of new drugs or nutritional modification.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine and Detroit Medical Center, 3990 John R., 3 Hudson, Detroit, MI 48201, USA.
authors.forename: Andreea
authors.initials: A
authors.lastname: Geamanu
authors.affiliation: Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Smiti V
authors.initials: SV
authors.lastname: Gupta
authors.affiliation: Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital of Michigan, Detroit, MI 48201, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Bauerfeld
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine and Detroit Medical Center, 3990 John R., 3 Hudson, Detroit, MI 48201, USA; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Lobelia
authors.initials: L
authors.lastname: Samavati
keywords: 1H NMR; Metabolomics; Sarcoidosis; TCA cycle; β-Oxidation