Characterization of the gut microbiome in Alzheimer disease and mild cognitive impairment among older adults in Uganda: A case–control study

Abstract

Alzheimer disease (AD) is associated with significant shifts in the gut microbiome and is characterized by reduced microbial diversity and changes in the abundance of specific taxa. These alterations can disrupt the gut-brain axis, leading to increased intestinal permeability ("leaky gut"), systemic inflammation, and oxidative stress. Such microbial changes are thought to contribute to neurodegenerative changes, as observed in AD and cognitive decline, thus emphasizing the role of the microbiome in aging-related neurological health. Our study in urban and rural population in Uganda recruited 104 participants aged 60 years and older, categorized into AD, mild cognitive impairment (MCI), and control groups based on Montreal Cognitive Assessment (MoCA) scores and ICD-11/DSM-V criteria. DNA was extracted from fecal samples using a QIAamp kit and polymerase chain reaction (PCR) products were sequenced using Nanopore. We used diversity indices, principal coordinate analysis (PCoA), permutational multivariate analysis of variance (PERMANOVA), and linear discriminant analysis effect size (LefSe) to identify significant microbial differences among groups. Gut microbiome diversity, as measured by the Chao1 and Shannon indices, was significantly reduced in patients with AD. The AD group had the lowest diversity compared to that of the control group (P < .05). PCoA showed distinct microbial shifts between patients with AD and controls, with MCI showing an intermediate profile. Genera such as Novosphingobium and Staphylococcus were more prevalent in the controls, whereas Hafnia-Obesumbacterium and Dickeya were more common in AD. Age-related changes included increases in Exiguobacterium and Carnobacterium and decreases in Acinetobacter and Klebsiella. Distinct microbial profiles were identified in the AD, MCI, and control groups, suggesting potential microbiome markers of cognitive impairment in the Ugandan population.