Abstract
Purpose
Emerging evidence has demonstrated that gut microbiome plays essential roles in the
pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS)
is a fatal neurodegenerative disease characterized by the progressive loss of motor
neurons. Treatment with the only drug approved by the US Food and Drug Administration
for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus,
there is an urgent need to develop novel interventions that for alleviate disease
progression and improve quality of life in patients with ALS. Here we present evidence
that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology.
Methods
We used G93A transgenic mice as a model of human ALS. The G93A mice show abnormal
intestinal microbiome and damaged tight junctions before ALS disease onset. The mice
were given 2% butyrate, a natural bacterial product, in the drinking water.
Results
In mice fed with butyrate, intestinal microbial homeostasis was restored, gut integrity
was improved, and life span was prolonged compared with those in control mice. At
the cellular level, abnormal Paneth cells—specialized intestinal epithelial cells
that regulate the host–bacterial interactions—were significantly decreased in the
ALS mice treated with butyrate. In both ALS mice and intestinal epithelial cells cultured
from humans, butyrate treatment was associated with decreased aggregation of the G93A
superoxide dismutase 1 mutated protein.
Implications
The findings from this study highlight the complex role of the gut microbiome and
intestinal epithelium in the progression of ALS and present butyrate as a potential
therapeutic reagent for restoring ALS-related dysbiosis.
Key words
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Article info
Publication history
Published online: January 24, 2017
Accepted:
December 28,
2016
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
