Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by interactions between environmental factors and genetic susceptibility.Sleep disorders such as circadian rhythm dysfunction (CD) significantly exacerbate neurodegenerative conditions such as Alzheimers disease and Parkinsons disease, and may also worsen ALS.The disturbed rhythm also promotes alterations in intestinal bacterial compositions, of which the abundance of cyanobacteria is considered an ALS risk factor.We tested the effects of CD on a mouse model of ALS, including examination of the changes in the gut microbiome related to the disease and CD.We found CD accelerated the onset and progression of ALS, as demonstrated by more rapid behavioral and motor symptom onset.We also found significantly increased motor neuron loss and astrocyte activation in the spinal cord.The composition of intestinal microflora varied during disease progression, demonstrating a particularly large increase in cyanobacteria shortly after disease onset.Thus, we believe one of the mechanisms through which CD accelerated disease onset and progression of ALS was promotion of proliferation of intestinal cyanobacteria in SOD1G93A ALS model mice, possibly at the expense of more beneficial phyla.Our study is the first to note the CD-cyanobacteria connection that represents a connected risk factor, and potential therapeutic target, for ALS.