A number of studies in recent years have shown that patients with Alzheimer's disease have a distinct gut microbiome composition in comparison to age-match peers. The gut microbiome changes with age, losing beneficial microbes and their production of metabolites necessary for tissue function, while gaining inflammatory microbes that contribute to the characteristic increase in chronic inflammatory signaling observed in older people. When it comes to the pro-inflammatory gut microbiome of Alzheimer's patients, it is still an open question as to whether this relationship exists because of the inflammation, in that inflammation drives the onset and progression of Alzheimer's disease, or whether other factors are at play. For example, a more pronounced age-related immune dysfunction could be a major contributing cause of both neurodegenerative conditions and shifts in the composition of the gut microbiome.
Alzheimer's disease (AD) is the most common form of dementia, characterized by an irreversible decline in cognitive function. The pathogenesis of several neurodegenerative disorders has been linked to changes in the gut microbiota, transmitted through the gut-brain axis. We set out to establish by case-control study methodology whether there were any differences in the composition and/or function of the gut microbiota between older resident adults in care homes with or without an AD diagnosis via analysis of the microbial composition from fecal samples. We performed primary analysis comparing controls (n = 19) against AD patients (n = 24).
These results indicate clear differences in the relative abundance of certain bacterial species and bacterial metabolites between care home residents with and without Alzheimer's disease that could be indicative of variable gut-brain axis activity. The AD cohort had significantly higher proportions of pro-inflammatory bacterial species and fewer 'beneficial bacteria'. We also found clear correlations between concentrations of beneficial bacterial metabolites and abundance of 'healthy bacteria'.
AD patients had increased levels of Escherichia/Shigella and Clostridium_sensu_stricto_1, which are linked to higher levels of gut inflammation. Escherichia/Shigella species can lead to higher levels of circulating lipopolysaccharide (LPS) and have been found in greater concentrations in the gut microbiota of individuals with mild cognitive impairment and in several prior AD studies. Certain strains of Escherichia/Shigella are known to form amyloid protein structures, known as curli, similar to those seen aggregating in the brains of AD patients. Although this is not definitively linked, it does raise one possibility as to how high levels of Escherichia/Shigella could potentially contribute to increased Alzheimer's pathology.
Similar to other studies, the AD cohort had decreased relative abundance of Bacteroides, Faecalibacterium, Blautia, and Roseburia species which are typically linked with good health. Both Roseburia and Faecalibacterium sp. are key butyrate producers and a significant decrease in the number of butyrate-producing bacteria, and subsequently butyrate, has previously been associated with AD. What cannot be determined from our data is whether the difference in microbiota is contributing to AD pathology or whether AD itself causes the microbial dysbiosis.
Link: https://doi.org/10.3390/geriatrics10020037
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