The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease

Abstract

Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer’s disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients’ quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease—cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-β aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer’s disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages.

Ischemic Brain Neurodegeneration

“…So far, two causes of Alzheimer’s disease have been intensively studied: amyloid plaques and neurofibrillary tangles, which, after more than a hundred years of research, did not explain the etiology of the disease. This was ultimately confirmed by research into anti-amyloid drugs, which showed that amyloid also has several beneficial properties, such as antibacterial, antioxidant, and neurotrophic effects [ 20 , 21 , 22 ]. In addition, the complete removal of amyloid can cause swelling and bleeding in the brain [ 22 ].…”

“…This was ultimately confirmed by research into anti-amyloid drugs, which showed that amyloid also has several beneficial properties, such as antibacterial, antioxidant, and neurotrophic effects [ 20 , 21 , 22 ]. In addition, the complete removal of amyloid can cause swelling and bleeding in the brain [ 22 ]. It should be noted that the causes of the disease should be investigated by looking at the body as a whole, and not just on one organ, that is, the brain.…”

“…It should be noted that the causes of the disease should be investigated by looking at the body as a whole, and not just on one organ, that is, the brain. Growing evidence points to the effect of changes in the gut microbiota on slow alterations in the brain and the subsequent development of Alzheimer’s disease symptoms [ 22 , 23 ]. Over the course of life, inflammation in the body also translates into the development of ischemic stroke and Alzheimer’s disease [ 15 , 22 , 23 ].…”

“…For this reason, the gut microbiome has recently been introduced as a new important “organ” of the human and animal body [ 15 , 23 ], as it can affect the early neuronal and immune stages, as well as metabolic abnormalities and various pathologies [ 4 ]. The influence on the intestinal microflora may be a new direction in research on neurodegeneration after ischemia and Alzheimer’s disease, and in the treatment of both diseases suggests that we must first focus on elucidating the etiology of Alzheimer’s disease while seeking simultaneously effective nutritional or pharmacological therapies [ 22 ]. These phenomena contribute to the death of neurons, loss of synapses, and glial dysfunction in the course of stroke and Alzheimer’s disease [ 8 , 13 , 19 , 22 ].…”

“…The influence on the intestinal microflora may be a new direction in research on neurodegeneration after ischemia and Alzheimer’s disease, and in the treatment of both diseases suggests that we must first focus on elucidating the etiology of Alzheimer’s disease while seeking simultaneously effective nutritional or pharmacological therapies [ 22 ]. These phenomena contribute to the death of neurons, loss of synapses, and glial dysfunction in the course of stroke and Alzheimer’s disease [ 8 , 13 , 19 , 22 ]. Inflammatory signals from the ischemic site further enhance intestinal dysbiosis, thus causing a pro-inflammatory loop.…”