Gut Microbial Composition and Short-Chain Fatty Acid Metabolism in Cognitively Unimpaired Adults Stratified by Amyloid-β Status.

Acetate was the predominant SCFA in fecal samples and demonstrated the most robust associations with microbial taxa.

• Fecal SCFAs were quantified using GC-MS in 87 cognitively unimpaired participants
• Microbial species were profiled by shotgun metagenomics
• Acetate showed more robust microbial associations than other SCFAs including butyrate, propionate, and valerate
• Associations were tested using nonparametric statistics and multivariable regression

Higher fecal acetate concentrations were positively associated with Bacteroides ovatus and Faecalibacterium prausnitzii.

• Associations between microbial species and acetate were evaluated using Spearman correlations
• Both Bacteroides ovatus and Faecalibacterium prausnitzii showed positive relationships with acetate levels
• Study included 87 cognitively unimpaired participants stratified by amyloid-β status

Lower fecal acetate levels were linked to species including Bifidobacterium animalis and Lachnoclostridium scindens.

• These species showed inverse relationships with acetate concentrations
• Associations were evaluated using Spearman correlations
• Multivariate ordinations were also used to evaluate microbial-SCFA links

Individuals with elevated amyloid-β burden exhibited more pronounced species-SCFA relationships compared to those with lower amyloid burden.

• Stratified analyses were conducted based on Aβ High vs. Aβ Low status
• A notable association between Bacteroides thetaiotaomicron and butyrate was identified specifically in the Aβ High group
• These patterns suggest subtle early gut microbial alterations linked to amyloid burden in cognitively unimpaired individuals

Multivariate ordination identified a significant overall coupling between SCFA profiles and microbial community structure.

• Multivariate ordination analyses were used to assess the relationship between overall SCFA profiles and microbial community composition
• The coupling was described as 'significant' across the full cohort of 87 participants
• This finding supports a systematic relationship between gut microbiome composition and SCFA metabolism

Mediation analysis suggested that an Oscillospiraceae species may be a potential intermediary linking valerate concentrations with amyloid-β status.

• Mediation analysis was used to explore potential indirect pathways between microbial taxa, SCFAs, and Aβ burden
• An unspecified species within the family Oscillospiraceae was identified as the potential mediator
• The mediation pathway linked valerate levels to Aβ status
• This represents an indirect rather than direct association

SCFA concentrations were not strongly influenced by demographic factors or APOE ε4 genetic status.

• Associations between SCFAs, demographics, and APOE ε4 status were tested using nonparametric statistics and multivariable regression
• Despite APOE ε4 being a major genetic risk factor for Alzheimer's disease, it did not show strong associations with SCFA levels
• Demographic variables also did not strongly predict SCFA concentrations

The study population consisted of 87 cognitively unimpaired adults stratified by cerebral amyloid-β burden.

• Participants were cognitively unimpaired, representing a preclinical AD population
• Stratification was based on Aβ burden (Aβ High vs. Aβ Low)
• Both fecal SCFA quantification (GC-MS) and shotgun metagenomics were performed on the same participants
• APOE ε4 status was also assessed