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

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...

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Published in:BMC neurology 2022-02, Vol.22 (1), p.62-19, Article 62
Main Authors: Kim, Harper S, Son, John, Lee, Donghwan, Tsai, Joy, Wang, Danny, Chocron, E Sandra, Jeong, Seongwoo, Kittrell, Pamela, Murchison, Charles F, Kennedy, Richard E, Tobon, Alejandro, Jackson, Carlayne E, Pickering, Andrew M
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - complications
Amyotrophic Lateral Sclerosis - diagnosis
Amyotrophic Lateral Sclerosis - pathology
Complications and side effects
Development and progression
Dysbiosis
Dysbiosis - complications
Gastrointestinal Microbiome
Humans
Intestines
Lou Gehrig’s disease
Microbiology
Microbiome
Mouth
Neurological research
Risk factors
RNA, Ribosomal, 16S - genetics
Severity of Illness Index
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Summary: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. 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). 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 
ISSN:1471-2377
1471-2377
DOI:10.1186/s12883-022-02586-5