Gut inflammation and dysbiosis in human motor neuron disease

Abstract

Amyotrophic lateral sclerosis (ALS) is a systemic disorder that involves dysfunction of multiple organs. Growing evidence has shown that neurodegenerative disorders with gut dysbiosis affect the central nervous system via pro-inflammatory mediators thus impacting gut-brain communications. We have demonstrated dysbiosis and increased intestinal permeability in the SOD1^G93A ALS mouse model. In this study, we comprehensively examined the human gut microbiome in stool samples and evaluated infection and markers of intestinal inflammation in five patients with ALS and motor neuron disorders. Five patients we studied all had alteration in their gut microbiome characterized by a low diversity of the microbiome, compared to healthy cohorts with relatively intact abundance. Firmicutes and Bacteroidetes are the two major members of bacteria at the phylum level. Low Ruminococcus spp occurred in three patients with low Firmicutes/Bacteroidetes (F/B) ratio. A majority of patients had signs of intestinal inflammation. This is the first comprehensive examination of inflammatory markers in the stool of ALS patients. Studies in gut health and microbiome related to the onset and progression of ALS may reveal novel therapeutic targets for disease modulation.

Keywords: ALS; bacteria; dysbiosis; inflammation; microbiome; motor neuron disease.

Figure 1

Representative reports of dysbiosis in three Amyotrophic lateral sclerosis (ALS) patients. The relative abundances of commensal bacteria at phylum level from patients and healthy controls were visualized by abundance bar plots. Reduced beneficial bacteria and shift of bacterial profile at the phylum level in ALS patients No. 1, 3 and 5, compared to the health cohort (n = 96). Firmicutes and Bacteroidetes are the two major members of bacteria at the phylum level. Firmicutes/Bacteroidetes (F/B) ratio was used as an indicator of dysbiosis. Three ALS patients all have low F/B ratio.