Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results.

Cristina Piras,Antonio Noto,Andrea De Giacomo,Vassilios Fanos,Fernanda Cristofori,Luigi Atzori,Martina Spada,Michele Mussap,Ruggiero Francavilla

doi:10.3390/metabo12020104

Abstract

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2–12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites—namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

Highlights

Autism spectrum disorder (ASD) is a group of pervasive neurodevelopmental conditions affecting more males than females in a ratio close to 3:1 [1]; ASD is characterized by complex, heterogeneous clinical phenotypes frequently associated with medical comorbidities [2,3]
27 children were enrolled in this study, with ASD and unaffected siblings (US)
Based on results that emerged from the orthogonal partial least squares (OPLS) model (Figure 5), we aimed to investigate any further metabolic change induced by the altered intestinal permeability

Summary

Introduction

Autism spectrum disorder (ASD) is a group of pervasive neurodevelopmental conditions affecting more males than females in a ratio close to 3:1 [1]; ASD is characterized by complex, heterogeneous clinical phenotypes frequently associated with medical comorbidities [2,3]. The overgrowth of specific microbial species and genera, together with the increased biosynthesis of harmful microbial metabolites, severely alters the integration of gut microbiota with the central nervous system (CNS), the immune system, and the host metabolism [9]. We aimed to explore the most relevant metabolic perturbations in a group of ASD children, compared with their healthy siblings, and to investigate whether alterations of the intestinal permeability in autistic children may induce specific perturbations in the urine metabolome

Objectives

Methods

Results

Discussion

Conclusion