The Oral Microbiome in Amyotrophic Lateral Sclerosis Shows Differentially Abundant Organisms in Limb Versus Bulbar Onset Disease: A Binational Study

Background and Purpose Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons leading to progressive disability and death.Approximately 10% of cases are caused by single-gene disorders with the remaining 90% of cases presumed to be caused by a combination of environmental and genetic factors.The microbiome (the ensemble of microorganisms that colonize body surfaces and organs) was recently identified for its importance in the pathogenesis of ALS.Methods In this study, we recruited 100 participants from two ethnically and geographically distinct sites (71 from Calgary, Canada, and 29 from Seoul, Republic of Korea) which included 59 ALS participants and 41 controls.All participants provided saliva samples for oral microbial analysis using 16S rRNA sequencing.Basic demographic information was collected from all participants, and ALS participants provided additional clinical information including site of disease onset, disease duration, and ALS Functional Rating Scale -Revised score. ResultsSignificant differences in beta diversity of the oral microbiomes were seen between limb-and bulbar-onset ALS participants.Two bacterial genera were differentially abundant between these groups, Bifidobacteriaceae Bifidobacterium was enriched in bulbar-onset cases, while Pasteurellaceae Haemophilus was enriched in limb-onset cases.No significant differences were found between ALS participants and controls, but there were significant differences when comparing participants from different sites of recruitment.Amongst household pairs (n= 35 pairs), ALS participants differed from control participants at the Seoul site.Conclusions Despite the cohort and household effects, our study identified differentially abundant organisms that may be important to the phenotypic variability of ALS and should be considered for future study.Our study provides novel insights into design for future multi-site microbiome research in ALS.