Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

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.

An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants

“…Recent studies highlight the importance of the microbiota-brain axis in PD 30 – 32 and its scientific anchors include: (1) a pro-inflammatory intestinal microbiota (characterized by low SCFA) can trigger intestinal barrier dysfunction, systemic inflammation, microglial activation, neuroinflammation, and oxidative stress (mechanisms contributing to neurodegeneration and alpha-synuclein misfolding) 33 – 36 ; (2) several diseases and disorders associated with increased risk of PD (e.g., metabolic syndrome, diabetes, inflammatory bowel disease, constipation) are associated with microbiota dysbiosis 37 – 40 ; and (3) use of levodopa is associated with reduced relative abundance of putative beneficial, SCFA-producing bacteria. Thus, it is plausible that a prebiotic intervention that alters the microbiota (and increases SCFA) could be an effective strategy to modify disease course, symptoms, or treatment success in PD patients 5 .…”

The Untapped Potential of Ginsenosides and American Ginseng Berry in Promoting Mental Health via the Gut–Brain Axis

“…This axis, relating the concepts of the intestinal microbiome, intestinal barrier function, endocrine and neurological factors, and mental health, is of great importance as new implications for a wide range of disease states have been emerging. For instance, links have been established between the gut-brain axis and neurological conditions, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and major depressive disorder [76,77], highlighting the need for more research evaluating strategies to target the gut-brain axis in these contexts effectively. Given the close link between host nutrition and the intestinal microbiome, nutritional and nutraceutical strategies are promising avenues to explore in helping treat these conditions.…”

Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis

“…The gut microbiota and its release of neurotransmitters, metabolites, and immune factors affect the central nervous system and brain function after stroke by affecting immune cell differentiation and accumulation and changing the levels of circulating antiinflammatory and proinflammatory cytokines (12). Modulation of the gut microbiome has the potential to prevent and treat stroke (13).…”