In:
BMC Neurology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-02-21)
Abstract:
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 〈 0.0001) and more severe symptoms ( r = 0.9470, P 〈 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B- ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood ( r = 0.9860, P 〈 0.0001) and greater disease severity ( r = 0.9842, P 〈 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P 〈 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. Conclusions We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.
Type of Medium:
Online Resource
ISSN:
1471-2377
DOI:
10.1186/s12883-022-02586-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2041347-6
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