Examining the complex Interplay between gut microbiota abundance and short-chain fatty acid production in amyotrophic lateral sclerosis patients shortly after onset of disease

Abstract

Abstract This study aimed to assess differences in the enteral microbiome of relatively recent-onset amyotrophic lateral sclerosis (ALS) patients (< 6–15 months since symptom onset) compared to healthy individuals, focusing on short-chain fatty acids (SCFAs) as potential mediators of host metabolism. We included 28 volunteers (16 ALS, 12 controls) with informed consent. No significant effect of ALS on alpha diversity (measuring the variety and abundance of species within a single sample, and indicating the health and complexity of the microbiome) was observed, but ALS patients had higher abundances of Fusobacteria and Acidobacteria. ALS subtypes influenced specific species, with increased Fusobacteria and Tenericutes in spinal ALS compared to bulbar ALS. ALS patients showed increased Enterobacter, Clostridium, Veillonella, Dialister, Turicibacter, and Acidaminococcus species and decreased Prevotella, Lactobacillus, and Butyricimonas. Correlations between species varied between ALS patients and healthy individuals and among ALS subtypes. No significant differences in SCFA concentrations were found, but spinal ALS samples showed a trend towards decreased propionate content. Relationships between SCFAs and phyla colonization differed by disease status. This study suggests distinct enteral microbiome characteristics in ALS patients, though the implications are unclear. Further research is needed to determine if these differences are causative or consequential and to explore their potential as diagnostic or therapeutic targets. The study also underscores the heterogeneity of microbiome constraints in ALS and the need for more research into ALS and SCFA metabolism.

Keywords

• Amyotrophic lateral sclerosis
• Enteral microbiome
• Short-chain fatty acids
• 16S sequencing
• Alpha-diversity
• Fusobacteria