Oxidative stress and gut microbiota's role in neurodegeneration: Review

By Louisa Richards

- Last updated on GMT

© image_jungle / Getty Images
© image_jungle / Getty Images
The complex interplay between oxidative stress, gut bacteria and epigenetics in neurodegenerative diseases highlights new areas for nutritional interventions, according to Romanian researchers.

In a new systematic review published in the journal Antioxidants,​ they focused on 161 studies from 2024 to capture the most recent developments and latest trends in research. The findings underscore the importance of the gut-brain axis in the onset of neurodegeneration.

Previous studies revealed the importance of oxidative stress, gut microbiota and epigenetic modifications as individual factors in neurodegeneration. The new review analyzes this evidence and reveals a complex interaction that it noted warrants further investigation and offers the potential for personalized medicine.

Oxidative stress and the brain

The new analysis revealed that gut microbiota and epigenetic modifications significantly influence redox balance, which plays a central role in the development of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. 

Redox homeostasis​ is the dynamic process of balancing reducing and oxidizing reactions within all cells, including those in the brain, to maintain their health. Antioxidants defend against reactive oxygen species, but disruptions in the balance lead to oxidative stress, a key driver of neurodegeneration.  

Gut microbiota produce metabolites that influence epigenetic modifications such as DNA methylation and histone modification, which in turn can alter the genes involved in oxidative stress and neuroinflammation.

These complex interactions confirm the importance of balanced gut bacteria and antioxidants in preventing degenerative diseases and expand the evidence for personalized nutritional strategies.  

Therapeutic strategies 

The study highlights several key nutritional interventions to support brain health. Hormesis​ is an adaptive response by the body that produces a positive effect at low doses of a stressor and a negative impact at higher doses. 

Leveraging the principles of hormesis with polyphenols and probiotics “presents a promising approach to enhancing cellular resilience, maintaining gut microbiota balance, and protecting against neurodegenerative processes,” the authors wrote. 

Similarly, nutritional epigenetics uses polyphenols such as resveratrol and curcumin and supplements such as S-adenosylmethionine (SAMe) to influence DNA methylation and histone modifications. This can mitigate oxidative stress and provide neuroprotection. 

The researchers suggest that antioxidant supplements such as vitamin C, E, and glutathione and gut support such as probiotics, prebiotics and synbiotics may help counteract oxidative stress and support the gut-brain axis.

Future directions

Current treatments for neurodegenerative diseases focus on symptoms and are mainly aimed at improving a person's quality of life. The FDA recently approved Eli Lilly’s Kisunla​, an amyloid plaque-targeting therapy, which was a significant step forward in disease-modifying drugs.

The reviewers conclude that exploring the interplay between oxidative stress, gut microbiota and epigenetic modifications could lead to a more holistic approach to treating degenerative diseases. 

“Clinical trials are needed to evaluate the efficacy of combining antioxidant therapies with microbiota-targeted interventions (e.g., probiotics) and epigenetic drugs,” they wrote.

Source: Antioxidants​ 2024, 13(9), 1062; https://doi.org/10.3390/antiox13091062
“Redox homeostasis, gut microbiota, and epigenetics in neurodegenerative diseases: a systematic review”
Authors: C. Munteanu et al.

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