Alzheimer’s disease (AD) is a neurodegenerative disorder that primarily affects the elderly population. Clinically, it is characterized by memory loss, cognitive decline, personality changes, and impaired executive functions. Amyloid-beta (Aβ) plaque accumulation, hyperphosphorylation of tau protein, neuroinflammation, oxidative stress, and widespread neuronal loss, particularly in the hippocampus and cortex, are the main pathological features of AD. Despite extensive research, effective disease-modifying treatments remain elusive, warranting the urgent need for novel therapeutic approaches. Gut-brain axis (GBA), a bidirectional communication network between the CNS and the gastrointestinal tract, involves neural pathways (such as the vagus nerve), endocrine signals, immune modulation, and microbial metabolites. The gut microbiota residing in the human intestine is responsible for maintaining gut integrity, regulating immune responses, producing neuroactive compounds, and modulating brain function. Gut dysbiosis, which is a disruption in the composition and function of gut microbiota, has been increasingly attributed to the development and progression of neurodegenerative diseases, including AD. Gut dysbiosis contributes to AD pathology through different mechanisms. An altered microbial profile enhances intestinal permeability (“leaky gut”), allowing the translocation of microbial products (such as LPS) into systemic circulation. These pro-inflammatory molecules can cross the blood-brain barrier (BBB), triggering neuroinflammation and exacerbating Alzheimer’s disease (AD) pathology, including Aβ deposition and tau hyperphosphorylation. Additionally, dysbiosis can impair the production of beneficial microbial metabolites (such as SCFAs), which have neuroprotective and anti-inflammatory properties. This altered microbial signaling may influence cognitive and emotional functions by changing the synthesis and regulation of neurotransmitters, such as serotonin, dopamine, and gamma-aminobutyric acid (GABA). Modulation of the compelling link between the gut microbiota and brain health, that is, the gut-brain axis, has emerged as a potential therapeutic strategy for AD. Several microbiota-targeted interventions are being explored to restore microbial balance and improve neurological outcomes. These include the administration of probiotics (beneficial bacteria), prebiotics (nondigestible food components that promote the growth of beneficial microbes), and synbiotics (a combination of both). Dietary modifications, particularly adherence to anti-inflammatory and fiber-rich diets such as the Mediterranean or MIND diets, have also shown potential in promoting gut and brain health. Another emerging intervention is fecal microbiota transplantation (FMT), where stool from a healthy donor is transferred to an AD patient to repopulate the gut with a healthy microbial community. The gut-brain axis represents a novel and promising frontier in understanding and managing Alzheimer’s disease. A gut microbiota-targeted approach to modulate systemic inflammation can augment neuroprotection and reduce cognitive decline. In the future, research efforts should focus on elucidating precise microbial products associated with AD and developing personalized microbiomes, thereby improving clinical outcomes and the quality of life of AD patients.

Alzheimer’s Disease Management Through the Gut-Brain Axis

章节
发表日期：

2026年

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Poonam Negi,
Nishtha Singh,
Pranshul Sethi

摘要

Alzheimer’s disease (AD) is a neurodegenerative disorder that primarily affects the elderly population. Clinically, it is characterized by memory loss, cognitive decline, personality changes, and impaired executive functions. Amyloid-beta (Aβ) plaque accumulation, hyperphosphorylation of tau protein, neuroinflammation, oxidative stress, and widespread neuronal loss, particularly in the hippocampus and cortex, are the main pathological features of AD. Despite extensive research, effective disease-modifying treatments remain elusive, warranting the urgent need for novel therapeutic approaches. Gut-brain axis (GBA), a bidirectional communication network between the CNS and the gastrointestinal tract, involves neural pathways (such as the vagus nerve), endocrine signals, immune modulation, and microbial metabolites. The gut microbiota residing in the human intestine is responsible for maintaining gut integrity, regulating immune responses, producing neuroactive compounds, and modulating brain function. Gut dysbiosis, which is a disruption in the composition and function of gut microbiota, has been increasingly attributed to the development and progression of neurodegenerative diseases, including AD. Gut dysbiosis contributes to AD pathology through different mechanisms. An altered microbial profile enhances intestinal permeability (“leaky gut”), allowing the translocation of microbial products (such as LPS) into systemic circulation. These pro-inflammatory molecules can cross the blood-brain barrier (BBB), triggering neuroinflammation and exacerbating Alzheimer’s disease (AD) pathology, including Aβ deposition and tau hyperphosphorylation. Additionally, dysbiosis can impair the production of beneficial microbial metabolites (such as SCFAs), which have neuroprotective and anti-inflammatory properties. This altered microbial signaling may influence cognitive and emotional functions by changing the synthesis and regulation of neurotransmitters, such as serotonin, dopamine, and gamma-aminobutyric acid (GABA). Modulation of the compelling link between the gut microbiota and brain health, that is, the gut-brain axis, has emerged as a potential therapeutic strategy for AD. Several microbiota-targeted interventions are being explored to restore microbial balance and improve neurological outcomes. These include the administration of probiotics (beneficial bacteria), prebiotics (nondigestible food components that promote the growth of beneficial microbes), and synbiotics (a combination of both). Dietary modifications, particularly adherence to anti-inflammatory and fiber-rich diets such as the Mediterranean or MIND diets, have also shown potential in promoting gut and brain health. Another emerging intervention is fecal microbiota transplantation (FMT), where stool from a healthy donor is transferred to an AD patient to repopulate the gut with a healthy microbial community. The gut-brain axis represents a novel and promising frontier in understanding and managing Alzheimer’s disease. A gut microbiota-targeted approach to modulate systemic inflammation can augment neuroprotection and reduce cognitive decline. In the future, research efforts should focus on elucidating precise microbial products associated with AD and developing personalized microbiomes, thereby improving clinical outcomes and the quality of life of AD patients.