Towards Treatments for Neurodegenerative Disease via Alteration of the Gut Microbiome
The balance of microbial populations making up the gut microbiome shifts with age, favoring potentially harmful, inflammatory microbes over those that produce beneficial metabolites. This is increasingly associated with the development of disease, and particularly with neurodegenerative conditions, though every age-related condition with a strong inflammatory component to its pathology is likely accelerated by the aging of the gut microbiome. There are ways to adjust the balance of populations to restore a more youthful configuration, such as fecal microbiota transplantation from a young donor, but the research community has yet to earnestly assess this type of approach as a potential treatment or mode of prevention for age-related neurodegeneration.
The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases.
This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.