Gut Microbiota Impact on Neurodegenerative Diseases

Emerging evidence indicates that the complex community of microorganisms inhabiting the gastrointestinal tract exerts profound influences on the onset and progression of neurodegenerative disorders. Through the microbiota–gut–brain axis, gut microbes modulate immune tone, metabolic signalling and neural function via metabolites, neurotransmitters and neuroendocrine pathways. Alterations in microbial diversity and composition have been linked to hallmark pathologies such as amyloid-β aggregation, tau hyperphosphorylation and sustained neuroinflammation. Experimental models reveal that shifts in microbial populations can impair microglial clearance of toxic proteins, destabilise the blood–brain barrier and influence central immune responses. Conversely, targeted manipulation of the gut ecosystem through diet, probiotics, prebiotics or faecal microbiota transplantation holds promise for ameliorating cognitive decline and motor symptoms across Alzheimer’s, Parkinson’s and other neurodegenerative conditions. Integrating mechanistic insights with clinical observations underscores the global significance of microbial interventions and paves the way for microbiome-based therapeutics to complement existing disease-modifying strategies.

Research from Nature Portfolio

Recent studies demonstrate that specific members of the Bacteroidota phylum suppress microglial phagocytosis, thereby exacerbating amyloid-β plaque accumulation in Alzheimer’s disease models, whereas antibiotic-mediated depletion of these taxa restores microglial clearance and reduces plaque burden. Foundational human investigations have characterised distinct gut microbial signatures in individuals with Alzheimer’s disease, reporting reduced diversity, altered Firmicutes-to-Bacteroidetes ratios and correlations between microbial taxa and cerebrospinal fluid biomarkers. Germ-free transgenic mouse studies have further shown that absence of gut microbiota leads to a marked reduction in cerebral amyloid pathology, while recolonisation with microbiota from diseased donors reinstates amyloid deposition, thereby implicating gut communities directly in protein misfolding and aggregation processes.

Gut Microbiota Impact on Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in gut microbiota impact on neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Gut microbiota: The assemblage of bacteria, archaea, viruses and fungi residing in the gastrointestinal tract.

Microbiota–gut–brain axis: Bidirectional network linking intestinal microbes and the central nervous system via neural, immune and metabolic routes.

Microglia: Resident immune cells of the central nervous system responsible for debris clearance and neuroinflammatory regulation.

Amyloid-β: Peptide fragment prone to aggregation into extracellular plaques, a pathological hallmark of Alzheimer’s disease.

Short-chain fatty acids: Microbial fermentation products such as acetate, propionate and butyrate that influence host immunity and neuronal signalling.

Blood–brain barrier: Selective endothelial interface that regulates the passage of molecules and cells between the bloodstream and brain tissue.

Faecal microbiota transplantation: Clinical procedure transferring stool-derived microbial communities from a healthy donor to a recipient to restore gut ecology.

Probiotics and prebiotics: Live microorganisms (probiotics) and nondigestible substrates (prebiotics) that confer health benefits by modulating gut microbial composition.

References

1. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduction and Targeted Therapy (2024).
2. Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models. Nature Communications (2024).
3. The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored. Molecular Neurodegeneration (2023).
4. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Scientific Reports (2017).
5. Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside. Translational Neurodegeneration (2024).