A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica

Abstract

Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR, multivariate statistics, one-way ANOVA, and univariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid cycle, and glycolysis. Metabolites altered in urine from MS patients were shown to be related to known pathogenic processes relevant to MS, including alterations in energy and fatty acid metabolism, mitochondrial activity, and the gut microbiota. Graphical AbstractCorresponding authors: Jay Reddy, School of Veterinary Medicine and Biomedical Sciences, Room 202, VBS, East Campus,

The future of NMR-based metabolomics

“…Metabolomics can provide information on the in vivo mechanism of action and to eliminate compounds likely to cause problems with side effects [43]. Recent studies have utilized metabolomics to search for biomarkers for colon cancer [44] and multiple sclerosis [45]. …”

Involvement of the Warburg effect in non‐tumor diseases processes

“…The activation of T cells and the accumulation of mononuclear phagocytes can promote destruction of the myelin sheath, ultimately leading to the formation of focal demyelinated lesions in MS (Lassmann, Bruck, & Lucchinetti, 2007). The alteration of energy metabolism is discovered in urine from MS patients (Gebregiworgis et al, 2016). Glycolysis intermediates lactate has the potential differentiating between healthy controls and MS patients.…”

Nontarget metabolomics profiling of neuromyelitis optica spectrum disorder

“…In this process, tyrosine is considered as an intermediate involved in the tricarboxylic acid cycle, as well as a metabolic regulator participating in the formation of ketone bodies. Teklab Gebregiworgis investigated glycolysis and ketone body synthesis and decomposition as vital metabolic pathways in NMOSD and multiple sclerosis (Gebregiworgis et al, ). Other research has shown that the brain comsumes a quarter of the whole body's glucose supply to sustain brain functioning, and when the blood gludcose supply fails to meet brain energy needs, the ketone body can alternatively serve as an energy source (Mathur, Lopez‐Rodas, Casanova, & Marti, ).…”

“…It was confirmed that the production of AQP-4 antibody accelerated the intracellular glutamate transport (Saikali, Cayrol, & Vincent, 2009) into ketone bodies (Marcos et al, 2016). In this process, tyrosine is in NMOSD and multiple sclerosis (Gebregiworgis et al, 2016). Other research has shown that the brain comsumes a quarter of the whole body's glucose supply to sustain brain functioning, and when the blood gludcose supply fails to meet brain energy needs, the ketone body can alternatively serve as an energy source (Mathur, Lopez-Rodas, Casanova, & Marti, 2014).…”