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Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy

    Shabnam Nohesara

    Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

    ,
    Hamid Mostafavi Abdolmaleky

    *Author for correspondence:

    E-mail Address: hamostafavi@yahoo.com

    Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

    Department of Surgery, Nutrition/Metabolism laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA 02215, USA

    ,
    Sam Thiagalingam‡

    Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

    Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

    ‡These authors contributed equally and co-directed this work

    Search for more papers by this author

    &
    Jin-Rong Zhou‡

    Department of Surgery, Nutrition/Metabolism laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA 02215, USA

    ‡These authors contributed equally and co-directed this work

    Search for more papers by this author

    Published Online:https://doi.org/10.2217/epi-2023-0342

    The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood–brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota–gut–brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.

    Plain language summary

    Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common age-related brain diseases. The incidence of AD is almost 20% in individuals over the age of 80 years, and the incidence of PD is 1–4% in individuals over the age of 60 years. Research scientists are studying various links among key factors involved in AD and PD pathogenesis, including diet, gut microbiota (communal bacteria living in our gut), neuroinflammation, epigenetic modifications (regulation of gene expression that is affected by environmental factors) and genetic changes to obtain greater insights into the mechanisms of disease development to design better therapeutics for these disabling diseases. The discovery of these relationships will provide opportunities to maintain favorable health via diet–microbiota–epigenetic modifications, since diet and surrounding environments play crucial roles in gut microbial alterations. Here, we discuss the interactions between destructive protein misfolding/aggregation in AD and PD, with neuroinflammation and epigenetic alterations that all are affected by nutrition, microbiota dysbiosis (imbalance), leaky gut (gut–blood barrier disruption) and internal or environmental toxins. We also present thought-provoking discussions and ideas about recent preventive/therapeutic approaches like special diets, probiotics, fecal microbiota transplantation and even specific antibiotics for preventing or improving neuropsychiatric symptoms in AD and PD.

    Tweetable abstract

    Alzheimer's and Parkinson's diseases are caused by genetic, epigenetic and gut microbiota shifts, and toxins. Microbiota dysbiosis affects gut and brain barriers, rising inflammation, epigenetic changes and protein misfolding. Diet, probiotics and fecal transfer hold promise for therapy.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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