The Gut Microbiota and Neurodegenerative Diseases: A Genetic and Epigenetic Approach

The gut microbiota, a complex and dynamic ensemble of microorganisms colonizing our digestive tract, plays a far broader role than simple digestion. Recent studies reveal its major influence on human health, particularly in the development of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and multiple sclerosis. These diseases, characterized by the progressive degradation of neurons, may partially originate from interactions between the microbiota, the immune system, and the brain via what is known as the gut-brain axis.

The gut microbiota produces metabolites, such as short-chain fatty acids, which modulate gene expression through epigenetic mechanisms, thereby influencing inflammation and neuronal health. For example, butyrate, a short-chain fatty acid, acts as an inhibitor of histone deacetylases, promoting anti-inflammatory gene expression. Conversely, an imbalance in the microbiota, or dysbiosis, can increase intestinal permeability, trigger inflammatory responses, and impair the blood-brain barrier, thereby contributing to neuroinflammation and neuronal degeneration.

In patients with Alzheimer’s disease, studies show a reduction in bacteria that produce short-chain fatty acids and an increase in pro-inflammatory species. These changes are associated with increased accumulation of amyloid plaques and worsening of cognitive symptoms. Fecal transplantation experiments in mice have confirmed that the microbiota from Alzheimer’s patients can induce cognitive disorders and brain inflammation in healthy animals. Similarly, in Parkinson’s disease, gut dysbiosis often precedes motor symptoms, suggesting that inflammation and microbial signals may initiate the degeneration of dopaminergic neurons.

Therapeutic approaches targeting the microbiota, such as probiotics, prebiotics, fecal transplantation, and nutritional interventions, are emerging as promising strategies. Clinical trials have demonstrated that certain probiotic strains improve cognitive functions in Alzheimer’s patients, while fecal transplantation has shown encouraging results in reducing motor symptoms in Parkinson’s patients. These interventions aim to restore a beneficial microbial balance, thereby reducing inflammation and improving brain health.

However, the individual variability of the microbiota highlights the need for personalized medicine. Genetic differences among individuals influence the composition of the microbiota and its response to treatments, making it essential to develop strategies tailored to each patient. Future research will need to focus on longitudinal studies and multi-omics approaches to better understand the interactions between the microbiota, genetics, and epigenetics, thus paving the way for more effective and targeted treatments against neurodegenerative diseases. These advances could transform the management of these diseases by integrating the microbiota as a key therapeutic target.

Bibliographie

Source de l’étude

DOI : https://doi.org/10.1007/s11011-026-01798-9

Titre : The relationship between gut microbiota and neurodegenerative diseases: a genetic and epigenetic perspective

Revue : Metabolic Brain Disease

Éditeur : Springer Science and Business Media LLC

Auteurs : Zeynep Betül Altan; Murat Ihlamur