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Basic Science and Pathogenesis.

Sithara Dissanayaka1,2, Thilini Jayasingh3, Hamid R Sohrabi4,5,6,7

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Summary
This summary is machine-generated.

Changes in gut bacteria and short-chain fatty acids (SCFAs) are linked to Alzheimer's disease (AD) progression. Modulating gut microbiota may offer a strategy to slow AD development by regulating SCFA levels.

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Area of Science:

  • Microbiome research
  • Neuroscience
  • Metabolomics

Background:

  • The gut-brain axis and short-chain fatty acids (SCFAs) are implicated in Alzheimer's disease (AD).
  • Understanding gut microbiota and SCFA changes throughout AD progression is crucial for disease insight.

Purpose of the Study:

  • To investigate alterations in gut microbiota composition and SCFA levels across different stages of AD.
  • To explore the relationship between specific gut bacteria and SCFA production in relation to amyloid-beta status and cognitive impairment.

Main Methods:

  • Examined gut microbiota and SCFA profiles in cognitively unimpaired (CU) individuals with low or high amyloid-beta (Aβ) and in a disease group (DG) with mild cognitive impairment or AD.
  • Utilized shotgun metagenomics for microbiota analysis and Gas Chromatography-Mass Spectrometry (GC-MS) for SCFA quantification.
  • Employed Spearman correlation and MaAsLin2 for association analyses between taxa and SCFAs.

Main Results:

  • Significant correlations were observed between major phyla (Firmicutes, Proteobacteria, Bacteroidetes) and SCFAs across all groups.
  • Specific associations included positive correlations between Firmicutes and butyric acid in CU Aβ Low and DG groups.
  • Distinct patterns emerged, such as negative correlations between Bacteroidetes and propionic acid in the DG group, and associations of Actinobacteria with butyric acid in the CU Aβ High group.

Conclusions:

  • Gut bacteria and SCFA profiles change dynamically during AD progression.
  • Key bacterial phyla and specific taxa are linked to SCFA levels, particularly butyric acid, highlighting their role in gut and brain health.
  • Targeting gut microbiota could be a potential therapeutic avenue for managing AD by influencing SCFA levels.