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Observational Study
. 2020 Feb 18:11:157.
doi: 10.3389/fimmu.2020.00157. eCollection 2020.

Host and Microbial Tryptophan Metabolic Profiling in Multiple Sclerosis

Lorenzo Gaetani  1 , Francesca Boscaro  2 , Giuseppe Pieraccini  2 , Paolo Calabresi  3 , Luigina Romani  4 , Massimiliano Di Filippo  1 , Teresa Zelante  4
Affiliations
Observational Study

Host and Microbial Tryptophan Metabolic Profiling in Multiple Sclerosis

Lorenzo Gaetani et al. Front Immunol. .

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is associated with demyelination and neuronal loss. Over recent years, the immunological and neuronal effects of tryptophan (Trp) metabolites have been largely investigated, leading to the hypothesis that these compounds and the related enzymes are possibly involved in the pathophysiology of MS. Specifically, the kynurenine pathway of Trp metabolism is responsible for the synthesis of intermediate products with potential immunological and neuronal effects. More recently, Trp metabolites, originating also from the host microbiome, have been identified in MS, and it has been shown that they are differently regulated in MS patients. Here, we sought to discuss whether, in MS patients, a specific urinary signature of host/microbiome Trp metabolism can be potentially identified so as to select novel biomarkers and guide toward the identification of specific metabolic pathways as drug targets in MS.

Keywords: indole-3-propionic acid; kynurenine; metabolite; microbiota; multiple sclerosis; signature; tryptophan; urine.

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Figures

Figure 1
Figure 1
In patients with relapsing-remitting multiple sclerosis (RRMS), we found a significantly lower urinary concentration of kynurenine (A) (median and interquartile range are reported) and kynurenine/tryptophan (K/T) ratio (B) (median and interquartile range are reported) than in healthy controls (HC). Additionally, a significant negative correlation between urinary K/T and the Expanded Disability Status Scale (EDSS) score at urine sampling was found (C). In RRMS patients in proximity (i.e., <30 days) to a clinical relapse, significantly higher urinary indole-3-propionic acid concentrations were found than in clinically stable RRMS patients (D) (median and interquartile range are reported). Moreover, urinary indole-3-propionic acid concentrations were positively correlated with the EDSS score at urine sampling (E). *p < 0.05.
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