Age-Related Changes in the Gut Microbiome and Alzheimer's Disease

Researchers here discuss potential links between (a) the detrimental changes that take place with age in the microbial populations of the gut and (b) the development of Alzheimer's disease. Given the present areas of interest in these fields of study, it seems likely that chronic inflammation is the primary point of overlap: changes in the gut microbiome promote inflammation, and inflammation drives the development of Alzheimer's.

One of the important factors that is influencing human health and attracting increasing attention of scientists during the last two decades is the gut microbiome. There are ~1,000 species and ~7,000 strains of bacteria that inhabit the human intestine, among which the most common are bacteria attributed to Firmicutes (51%) and Bacteroidetes (48%). However, over the last 15 years, the functions of the intestinal microbiome have been revised owing to the establishment of a direct link between density and species composition of the intestinal microbiome and a number of pathological conditions including diabetes, obesity, and cardiovascular diseases. These diseases, in turn, are the established risk factors for the development of Alzheimer's disease (AD), and there is data indicating that gut microbiome influences brain functions. Moreover, recent studies have revealed the significant differences in quantity and quality of gut microbiome in AD patients compared to mentally healthy individuals of the same age.

On the other hand, negative lifestyle aspects, among people living in our modern societies, are also considered important risk factors for the development of AD. The most striking result is that radical increases in Alzheimer's disease in Japan and substantial increase in developing countries are associated with changes in national diets. Furthermore, there are many undesirable lifestyle factors in the modern society that may contribute to AD development. These factors include unhealthy diet, lack of sleep, circadian rhythm disturbance, chronic noise, sedentary behavior etc., and, in turn, gut microbiome is highly sensitive to these factors. From this point of view, studying the links between modern lifestyle, gut microbiome and Alzheimer's disease is an important task that requires special attention.

Reducing the number and species diversity of many beneficial anaerobes such as Bifidobacterium and Lactobacillus, as well as a shift in the diversity of the intestinal microbiota toward pathogenic microorganisms, results in changes in local intestinal chemical and immunological parameters and induces the translocation of the gut bacteria into lymphoid tissue. These factors contribute to an increase in permeability of the intestinal barrier and blood-brain barrier and the penetration of pathological microflora and their metabolites into the brain.

On the other hand, intestinal bacteria are able to excrete functional amyloid peptides and lipopolysaccharides (LPS) in large quantities. Amyloid peptide in bacteria contributes to various physiological processes on the surface of bacterial cells, such as biofilm formation, adhesion, interaction with other bacterial and eukaryotic cells, etc. Its structure and biophysical properties are similar to human pathological amyloid. In addition to the amyloid peptide, many intestinal bacteria secrete LPS. LPS are the main components of the outer cell wall of gram-negative bacteria and, in the case of penetration from the intestinal cavity into the bloodstream, can cause neuroinflammatory reactions. Published data indicates that the LPS level in the blood plasma of patients suffering from AD is three times higher than the physiological age norm.


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