Editors' ChoiceMultiple Sclerosis

Let’s break it down: Metabolomics and pediatric MS

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Science Translational Medicine  31 Oct 2018:
Vol. 10, Issue 465, eaav3896
DOI: 10.1126/scitranslmed.aav3896

Abstract

Tryptophan metabolic profile is associated with multiple sclerosis risk and disease severity in children.

Multiple sclerosis (MS) is an immune-mediated condition characterized by focal areas of central nervous system (CNS) demyelination, manifested by episodes of sensory loss or weakness. In its most common form, symptoms improve between disease flares, but neurologic dysfunction may accumulate, leading to progressive physical and cognitive impairments. MS is best known as a disease of adults, but children may also be affected. Although children tend to recover from each MS flare more completely than adults, they accrue more disability over time.

MS has distinctive—albeit variable—clinical features, yet its pathogenesis remains unclear. In patients with an underlying genetic susceptibility, a dysregulated, self-directed immune response may be awakened by unknown environmental factors. Infection, vitamin D levels, and diet have all been postulated as possible triggers. Recently, tryptophan (TRP), an amino acid metabolized by both endogenous and gut microbial–derived pathways, has come under scrutiny as a potential disease modifier in adult MS.

Nourbakhsh et al. investigate whether a similar effect can be detected in pediatric MS. Affected children and matched controls underwent global metabolomics serum testing, and subsequently two larger cohorts underwent targeted analyses of TRP metabolism. In all three groups, higher serum TRP levels were associated with reduced risk of MS. In the global metabolomics group—but not in the cohorts who underwent targeted analysis—higher levels of gut microbial–derived TRP metabolites were individually associated with lower relapse rate, reduced physical disability, and better cognition. In contrast, higher levels of an endogenous TRP metabolite coincided with higher relapse rate. The authors also found an inverse association between abundance of microbial genes involved in TRP metabolism and MS relapse risk in a subset of patients who provided stool samples.

This study is exploratory in nature, and only the association with serum TRP level was maintained across all three groups of patients. Together with related investigations, however, this work reinforces the complex association between metabolism and neuroinflammation. For pediatric MS, a condition that has the potential to be permanently disabling, dietary TRP intake and the gut microbiome are therapeutic targets worthy of further study.

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