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Guillermou's avatar
Guillermou
2d

This review highlights the evolving notion of the gut-brain axis (GBA) as an equally sensitive pathological marker of neurodegenerative diseases (NDDs), particularly Alzheimer's disease, Parkinson's disease, multiple sclerosis, and chronic stroke. Furthermore, GBA represents a potent therapeutic target for the treatment of NDDs. 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, manifesting primarily as extrapyramidal and pyramidal movement disorders, with neuropathological evaluation at autopsy as the gold standard for diagnosis. NDDs are a global health problem; in the US alone, 12 million Americans will suffer from NDDs by 2030. While the etiology may vary, the gut microbiome serves as a key underlying element in the development and prognosis of NDDs. In particular, an associated microbiome Inflammation affects neurodegenerative disorders (NDDs). Conversely, sequestering this inflammatory microbiome by correcting the dysbiotic state of the gut can generate therapeutic effects on NDDs. To this end, treatment with bacteria that produce short-chain fatty acids, the main metabolites responsible for maintaining intestinal homeostasis, improves 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.

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. Early neurobehavioral deficits accompany epigenome remodeling by environmental factors such as smoking, alcohol, stress, and pesticide exposure.

The pathogenesis of Alzheimer's disease coincides with a microbiota Dysfunctional gut (Figure 2). Irritable bowel syndrome, characterized by an altered gut microbiota, is one of the main pathophysiological factors in Alzheimer's disease (AD). Bacteria that invade the gut microbiome have the capacity to excrete large amounts of amyloid and lipopolysaccharides, which can contribute to AD pathology. Furthermore, because AD is an age-related disorder, the gut-brain barrier (GBB) and the gastrointestinal tract epithelium become more permeable with age, allowing polysaccharides and amyloid to access the brain, readily causing inflammation. Such age-induced compromise of the BBB and gut suggests that the GBA may be involved in the early stages of proteinopathy and inflammation associated with AD.

https://www.mdpi.com/1422-0067/23/3/1184 (2022)------------------------------------------------------------

Physical and psychological stress alters the activity of the gut-brain axis, which can cause dysfunction. of the intestinal barrier, which, in turn, can induce cognitive and mood impairments through exacerbated inflammation and increased permeability of the blood-brain barrier (BBB)

https://www.sciencedirect.com/science/article/abs/pii/S0889159122000277 (2022)-----------------------------

Alzheimer's disease is the most prevalent type of dementia affecting the elderly, characterized by beta-amyloid (Aβ) plaques and tau neurofibrillary tangles that cause intellectual impairment, neuroinflammation, and memory decline. Neuroinflammatory variants such as IL-1β, TNF-α, and IL-6 have been identified in patients with Alzheimer's disease. Previous research has revealed that amyloid functions as an antimicrobial peptide in the brain. The gut microbiota is considered a dynamic factor in the etiology of the disease due to the presence of microbiota-derived metabolites in the cerebrospinal fluid of patients. Several studies have demonstrated the importance of gut microbes in host cognition and the dysbiosis associated with neurodegeneration in old age. Dysbiosis in the gut microbiota leads to the production of amyloid and lipopolysaccharides (LPS), which alter the permeability of the digestive tract and also disrupt the function of the blood-brain barrier.

A β-peptide has antibacterial properties and is part of the innate immune system that protects against pathogenic microorganisms. Furthermore, bacterial amyloid exhibits chemical similarity to human Aβ-peptide, leading to Aβ-peptide denaturation and accumulation, propagation of the gut-brain axis pathway, and activation of microglial cells. Bacterial-derived amyloids, such as prions, tau, α-syn, and other amyloids, have been reported to act as initiators and assemble with host amyloids in patients with Alzheimer's disease.

Amyloids derived from bacteria, such as prions, tau, α-syn, and other amyloids, have been reported to act as initiators and assemble with host amyloids in patients with Alzheimer's disease. https://www.sciencedirect.com/science/article/pii/S0753332222013476 (2022)

https://www.mdpi.com/1422-0067/26/18/8905 (2025)

https://www.nature.com/articles/s44400-025-00048-6 (2025)

https://journals.sagepub.com/doi/abs/10.1177/13872877261441247 (2026)

https://link.springer.com/article/10.1007/s00702-026-03126-y (2026)

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Sabina's avatar
Sabina
2d

Thank you Dr Mercola; I've recently read how Butyrate is essential for gut health and your article confirms it.

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