Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis

Lu Chen,Mingming Zhao,Yong Chen,Lemin Zheng,Dongsheng Fan

doi:10.1038/s41598-020-72184-3

Abstract

To compare the plasma concentrations of trimethylamine N-oxide (TMAO) and its precursors in amyotrophic lateral sclerosis (ALS) patients, their spouses and healthy controls and to find associations between gut microbiota metabolites and ALS. ALS patients were recruited at Peking University Third Hospital from January 2015 to December 2018. Information was collected from their spouses at the same time. Age and gender matched healthy controls were recruited from individuals who visited the physical examination center for health checkups. Blood samples were collected after at least 4 h of fasting. Concentrations of the metabolites were quantified using stable isotope dilution liquid chromatography–tandem mass spectrometry. Group differences were analyzed using parametric and nonparametric tests, as appropriate. In this study, 160 patients with ALS were recruited. In these patients, 63 were compared with their spouses, 148 were compared with age and gender matched controls, and 60 were compared with both their spouses and heathy controls in the same time. The carnitine concentration was significantly higher in patients than in their spouses, while there were no significant differences in the concentrations of other metabolites. The carnitine and betaine concentrations were higher, while the choline, TMAO and butyrobetaine concentrations were lower in ALS than in healthy controls. The concentrations of the metabolites in the spouses were more similar to the ALS patients rather than to the healthy controls. In the ALS group, the plasma concentrations of carnitine, betaine, choline and TMAO were inversely related to the severity of upper motor neuron impairment. The TMAO metabolic pathway of the gut microbiota is disturbed in both ALS patients and their spouses, which might suggest that the changes in the gut microbiota occurred before disease onset. The negative correlations between the involvement of UMNs and the concentrations of the metabolites might suggest that the inhibition of this metabolic pathway might lead to a better prognosis in ALS patients.

Highlights

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that involves upper and lower motor neurons[1,2,3,4,5,6,7,8]
This study focused on the relationship between the metabolites of the gut microbiome and amyotrophic lateral sclerosis (ALS)
The concentrations of trimethylamine N-oxide (TMAO) and its precursors in both patients with ALS and their spouses were significantly different from the age and gender matched healthy controls

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that involves upper and lower motor neurons[1,2,3,4,5,6,7,8]. A recently published study confirmed that the gut microbiota was significantly changed in ALS S OD1G93A mouse models compared with controls and that the disease was exacerbated under germ-free or wide-spectrum antibiotic treatment c onditions[19]. L-carnitine and TMAO are believed to be causes of atherosclerosis[20,21], Kira et al confirmed that the oral administration of L-carnitine may delay the onset and progression of ALS and extend the life span of S OD1G93A mice[13,22]. The effectiveness of carnitine treatment suggested that TMAO and its related metabolites may play important roles in the onset and progression of ALS. We compared the concentrations of TMAO and its precursors in the plasma of patients with ALS, their spouses and age and gender matched healthy controls, and tried to find associations between the metabolites of the gut microbiota and ALS

Methods

Results

Conclusion