Tuesday, 9 February 2016

See a man about a horse

J Proteome Res. 2016 Feb 5;15(2):659-666. Epub 2016 Jan 27.

A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica.


Gebregiworgis T, Nielsen HH, Massilamany C, Gangaplara A, Reddy J, Illes Z, Powers R.


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.

Figure: Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery.

It's a passing joke in the group about Prof G's propensity to add urine to the list of things collected in clinical trials, stemming from his Phd where urine featured heavily. But there may now be a role for urine studies, in fact I can attest to our group having the largest collection known to man. I remember distinctly when a batch of them had broken in a chest freezer and everyone knows that as the student you're on toilet-cleaning duty! Let's just say you have to first defrost the freezer...

But what does the simple urine have to offer? In reality urine is a complex mixture and contains many metabolites; which are small (<1500 Da) end products of enzymatic reactions or protein activity that vary based on genetics, environmental stress, toxins or drugs. Thus, a disease which causes an alteration in the way the body functions is expected to have a unique metabolic profile or fingerprint. NMR metabolomics is the investigation of urine metabolites using NMR technique which allows the simultaneous detection of a number of metabolites in a complex mixture such as urine without the need for first separating them.

In this study, the authors observed alterations in the pathways involved in energy generation, specifically glycolysis and in the synthesis and degradation of ketone bodies. The brain has high energy requirements using 25% of total glucose, but also uses ketone bodies as an alternative source of energy. Thus, what we may be observing is an alteration in energy generation in MS. This feeds well into the idea that MS is linked to mitochondrial defects, which would be expected to alter energy generation. The authors also found alterations in the creatine/phosphocreatine/creatine kinase system, which is critical for maintaining energy levels in the brain, and in propionate (short chain fatty acid) metabolism, meaning that there may be some lipid dysfunction in MS. Last but not least, they report changes in hippurate, a microbial cometabolite. Propionate is also a metabolite of the gut microbiota. So we are not alone - or are we?