Abstract
Human lifestyle and dietary behaviors contribute to disease onset and progression. Neurodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time. NDDs are a worldwide health problem; in the US alone, 12 million Americans will suffer from NDDs by 2030. While etiology may vary, the gut microbiome serves as a key element underlying NDD development and prognosis. In particular, an inflammation-associated microbiome plagues NDDs. Conversely, sequestration of this inflammatory microbiome by a correction in the dysbiotic state of the gut may render therapeutic effects on NDDs. To this end, treatment with short-chain fatty acid-producing bacteria, the main metabolites responsible for maintaining gut homeostasis, ameliorates the inflammatory microbiome. This intimate pathological link between the gut and NDDs suggests that the gut-brain axis (GBA) acts as an underexplored area for developing therapies for NDDs. Traditionally, the classification of NDDs depends on their clinical presentation, mostly manifesting as extrapyramidal and pyramidal movement disorders, with neuropathological evaluation at autopsy as the gold standard for diagnosis. In this review, we highlight the evolving notion that GBA stands as an equally sensitive pathological marker of NDDs, particularly in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and chronic stroke. Additionally, GBA represents a potent therapeutic target for treating NDDs.
Highlights
Neurodegenerative diseases (NDDs) are commonly defined as pathologies that lower normal brain function, usually accompanied by brain tissue atrophy and lower cognition capacity with a tendency to worsen with chronicity [1,2] NDDs manifest as chronic and aging brain pathologies, the exact timing for a brain pathology to turn into a neurodegenerative aberration remains not well understood
Low birth weight, obesity with coronary heart disease, and deterioration in neurocognitive development in adult life, with maternal smoking exacerbating this phenotype [28,29,30,31]. Neurological disorders, especially those presenting with neurodegeneration, have been associated with harmful environmental factors identified in childhood; in particular, an unbalanced diet that alters early gene expression leads to epigenetic changes that manifest in adulthood [28]
Transplanting stem cells into the gut of preclinical models of NDDs reduces the inflammatory microbiome not just in the gut and in the brain accompanied by improvement in neurological functions
Summary
Human developmental stages represent a key period that may affect health in adulthood [28,29,30]. Low birth weight, obesity with coronary heart disease, and deterioration in neurocognitive development in adult life, with maternal smoking exacerbating this phenotype [28,29,30,31] Neurological disorders, especially those presenting with neurodegeneration, have been associated with harmful environmental factors identified in childhood; in particular, an unbalanced diet that alters early gene expression leads to epigenetic changes that manifest in adulthood [28]. In stroke, lactation protects the maternal brain against ischemic insult partly through angiogenic and neurogenic remodeling processes [37] These findings suggest that epigenetics in early life, or when recapitulated during pregnancy, may play a significant role in adult health, regulating the brain capacity to undergo repair or neuroregeneration
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