Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome

Abstract

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.

Acidified drinking water improves motor function, prevents tremors and changes disease trajectory in Cln2R207X mice, a model of late infantile Batten disease

“…Accumulated evidence indicates that the gut microbiome plays a critical role in the development of neurodegenerative and neurological diseases 16 . We have previously shown that in comparison to WT mice, the gut microbiota composition of Cln2 R207X mice is significantly altered 17 .…”

Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation

“…The Western diet has sped up changes in the human microbiome. Highly processed foods, animal products, and sugars alter the microbiome to cause intestinal inflammation [ 7 ].…”

“…A link has been found between the composition of the intestinal microbiota and several diseases and symptoms, such as pain, cognitive function, and neurodegenerative diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. This link suggests not only that the gut microbiota composition can serve as the basis 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 these diseases [ 7 ]. The composition, density, and diversity of our individual microbiomes are dynamic and affected by multiple factors.…”

“…The composition, density, and diversity of our individual microbiomes are dynamic and affected by multiple factors. Few of these factors including lifestyle, diet, geography, genetics, immune system, history of infections, and a plethora of environmental components can be modified [ 7 ].…”

Evaluation of the Impact of Near-Infrared Multiwavelength Locked System Laser Therapy on Skin Microbiome in Atopic Dogs

“…The beneficial effects of PBM in reducing inflammation and edema, restoring blood flow, improving tissue healing, and inducing analgesia have been widely demonstrated in humans [ 16 , 17 , 18 ]. Moreover, there is also growing evidence that PBM may influence the microbiome [ 19 , 20 , 21 , 22 , 23 , 24 ]. Interestingly, Bicknell and colleagues demonstrated that PBM delivered to the abdomen of mice produced a significant change in the gut microbiome and, in humans, they observed a change in the microbiome in Parkinson patients after PBM treatment [ 21 , 22 ].…”