Objective:

To determine the role of specific microbial populations in modulating the disease progression in SOD1 mice using specific antibiotics.

Background:

While there has been significant progress in understanding the genetic underpinnings of ALS, greater than 90% of cases are sporadic and environmental factors that modulate genetic disease risk are being identified. The gut microbiota contribute to disease pathogenesis of several neurological disorders including Parkinson's disease, multiple sclerosis, and Alzheimer’s disease. We found that high-dose, broad spectrum antibiotics worsened survival in SOD1 mice, suggesting the gut microbiome as a whole protects against disease progression in ALS, but little is known about individual microbes.

Design/Methods:

To deplete specific microbial populations, we administered low dose oral vancomycin or metronidazole to SOD1 mice and measured survival, motor function, and neurological score.

Results:

We found that vancomycin improved survival (p=0.02) and neurological function, implying that the bacterial populations suppressed by the vancomycin have a deleterious effect on disease progression, whereas metronidazole did not impact disease progression. We are currently sequencing the microbiota to study the bacterial populations suppressed by vancomycin vs. metronidazole to identify microbes that may worsen progression in SOD mice.

Conclusions:

While high-dose antibiotics that deplete the microbiota worsen progression, we found for the first time that a narrower-spectrum approach of administering vancomycin alone can improve survival. This suggests that specific microbial manipulation may be used to modulate the disease course for the treatment of ALS, and that antibiotic selection may be important in the treatment of infections in ALS patients.