The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

Qianqian Zeng,Jinxia Zhou,Jiao Yuan,Kangzhi Chen,Qiao Liao,Jie Shen,Ke Lu,Fangfang Bi

doi:10.1038/s41598-020-69845-8

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists. The accumulating evidence has indicated the association between gut microbiota and various neurological diseases. Thus, to explore the potential role of gut microbiome in ALS, 20 patients diagnosed with probable or definite ALS and 20 healthy controls were enrolled and their fecal excrements were collected. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in microbial structure of ALS patients, where Bacteroidetes at the phylum level and several microbes at the genus level were up-regulated, while Firmicutes at the phylum level and Megamonas at the genus level were down-regulated compared to healthy controls. Additionally, decreased gene function associated with metabolic pathways was observed in ALS patients. The metagenomics further demonstrated the discrepancies in microflora at the species level and relevant metabolites thereof were also revealed when combined with metabolomics. In conclusion, the altered composition of the gut microbiota and metabolic products in ALS patients provided deeper insights into the pathogenesis of ALS, and these biomarkers might be established as potential therapeutic targets which deserve further exploration.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists
Twenty ALS patients and an equal number of age-matched healthy controls were recruited, in which each group consisted of 8 females and 12 males
ALS is a neurodegenerative disease characterized by the presence of progressive degeneration of both upper motor neurons and lower motor neurons[26]

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists. To explore the potential role of gut microbiome in ALS, 20 patients diagnosed with probable or definite ALS and 20 healthy controls were enrolled and their fecal excrements were collected. Decreased gene function associated with metabolic pathways was observed in ALS patients. The altered composition of the gut microbiota and metabolic products in ALS patients provided deeper insights into the pathogenesis of ALS, and these biomarkers might be established as potential therapeutic targets which deserve further exploration. The microglia and astrocytes in central neuronal system were attested to be regulated by metabolites derived from symbiotic gut microbes, the pathway of which inhibited the neuroinflammation and neurodegeneration in the experimental autoimmune encephalomyelitis model[18]

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Conclusion