Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset

  • Harper S. Kim (Creator)
  • John Son (Creator)
  • Donghwan Lee (Creator)
  • Joy Tsai (Creator)
  • Danny Wang (Creator)
  • Estrella S Chocron (Creator)
  • Seongwoo Jeong (Creator)
  • Pamela Kittrell (Creator)
  • Charles F. Murchison (Creator)
  • Richard E. Kennedy (Creator)
  • Alejandro Tobon (Creator)
  • Carlayne E Jackson (Creator)
  • Andrew M. Pickering (Creator)



Abstract Background Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. Methods ALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). Results sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P
Date made available2022

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