The Aging Gut Microbiome in the Context of Alzheimer's Disease

The gut microbiome changes with age. The complex balance of microbial species shifts in an unfavorable direction, and with it comes ever greater chronic inflammation alongside a loss of beneficial metabolite production. It remains an open question as to how much of the inflammation of aging, disruptive of tissue function and health, is caused by the gut microbiome. Identifying mechanisms is one thing, figuring out their relative importance quite another. The only practical way to achieve that goal is to change just the one mechanism in isolation of all the others, and observe the results.

In the case of the aging gut microbiome, there are a few comparatively simple approaches demonstrated to reverse age-related changes for a protracted period of time. The most proven is fecal microbiota transplantation from a young individual to an old individual. In short-lived species, this resets the microbiome, improves health, and extends life. It is not an approved human therapy in the US, but is nonetheless often used for treatment of conditions in which pathological bacteria overtake the intestines, both by physicians, and by patients taking matters into their own hands. Setting aside the question of how to screen for microbes that might cause issues to an older individual, it is a simple procedure.

At some point the clinical community will get around to running formal trials of fecal microbiota transplantation as a means to improve health in later life, but since intellectual property will likely be hard to produce and defend for this type of therapy, we shouldn't hold our breath waiting for that to happen. Progress, and funding for small-scale trials, is more likely to emerge from philanthropic initiatives. Initiatives of this sort have yet to exist for this approach to aging, unfortunately.

The Potential Role of Gut Microbiota in Alzheimer's Disease: From Diagnosis to Treatment

Alzheimer's disease (AD), which affects approximately 50,000,000 people worldwide, is the most frequent cause of dementia, constituting a real global health problem. The disease is characterized by the progressive deposition of beta amyloid (Aβ) plaques and tangles of hyperphosphorylated tau neurofibrils, leading to neuroinflammation and progressive cognitive decline. Synaptic dysfunction and neuronal death are at least in part due to the excessive or non-resolving activation of the immune response and any infections or traumatic events affecting the brain (traumatic brain injury) can interfere with central immune homeostasis and accelerate the progression of the disease.

Although several hypotheses have been formulated about the causes of AD pathogenesis and progression, both the onset and the evolution of the disease remain not entirely clear. Therefore, although different therapeutic options have been proposed, many have failed in clinical trials and have not been found to produce significant benefits. It is widely thought that an early diagnosis could be essential to act at the earliest disease stages, but effective and reproducible biomarkers are still far from clinical application.

In recent years, the gut microbiota brain axis (GMBA) has been at the center of biomedical research and it has been suggested as a potential therapeutic target for disorders affecting the central nervous system, including AD. The term "gut microbiota" refers to the commensal microbial community that colonizes the gastrointestinal tract and is constituted by bacteria, fungi, archaea, viruses, and protozoans living in symbiotic relationship with our intestine. Thanks to their active role in regulating host's homeostasis and disease, they are becoming more and more important in the pathogenetic mechanisms of neurodegenerative disorders, such as AD.

Indeed, even though for a long time it was believed that the brain was a totally isolated organ, recent evidence shows that the gut microbiota is at the center of a bidirectional communication between intestine and brain, the so-called microbiota gut-brain axis. This interplay involves the central nervous system (CNS), the autonomic nervous system, the enteric nervous system (ENS), and the hypothalamus-pituitary-adrenal axis (HPA), and it has been reported to be implicated in a number of physiological and pathological processes such as satiety, food intake, glucose metabolism and fat metabolism, insulin sensitivity, and stress. Although the mechanisms underlying this interaction are not fully understood, targeting the microbiota might represent a new diagnostic and therapeutic strategy in AD and in other neurodegenerative diseases.

However, despite several published papers having reviewed possible microbiome-based therapies, to our knowledge a comprehensive view of gut microbiota-based diagnostic and therapeutic approaches is still lacking. Here, based on the main studies addressing gut microbiota dysregulation in AD, we discuss how the microbiota-derived biomarkers might be exploited for early disease detection, and we review the potentiality of probiotics, prebiotics, diet, and fecal microbiota transplantation as complementary therapeutic options for this devastating and progressive disease.

Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.