Progress and Perspectives on the Estrogen–Microbiota–Brain Axis in Alzheimer’s Disease

Nov 26, 2025Neurochemical research

Updates on How Estrogen, Gut Bacteria, and Brain Interact in Alzheimer's Disease

AI simplified

Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Alzheimer's disease is influenced by genetic, metabolic, environmental, and sex-specific factors.

The estrogen-gut microbiota-brain (EGMB) axis connects hormonal regulation, gut microbes, and cognitive health.
Estrogen has neuroprotective effects by affecting brain plasticity, reducing oxidative stress, and modulating inflammation.
The decline of estrogen during menopause may increase vulnerability to Alzheimer's disease.
Gut dysbiosis and changes in microbial metabolites, such as short-chain fatty acids, can lead to brain dysfunction.
Estrogen influences the composition of gut bacteria and the availability of its own bioactive forms.
Integrating hormone replacement therapy with microbiota-targeted treatments may enhance neuroprotection against Alzheimer's.

AI simplified

Alzheimer's disease (AD) is a progressive neurodegenerative disorder shaped by genetic, metabolic, environmental, and sex-specific factors. Emerging evidence highlights the estrogen-gut microbiota-brain (EGMB) axis as a critical framework linking endocrine regulation, microbial activity, and cognitive outcomes. Estrogen exerts neuroprotective effects by modulating synaptic plasticity, oxidative stress, amyloid and tau pathology, and neuroinflammation, while its decline during menopause increases AD vulnerability. Parallel to this, gut dysbiosis and altered microbial metabolites, particularly short-chain fatty acids (SCFAs) and secondary bile acids (sBAs), contribute to barrier dysfunction, chronic inflammation, and synaptic impairment. Importantly, estrogen remodels microbial composition and metabolite profiles, whereas microbial β-glucuronidase (β-GUS) activity sustains estrogen bioavailability, establishing a reciprocal regulatory loop. Preclinical studies demonstrate that depletion of gut microbiota diminishes estrogen's protective effects, underscoring the central role of microbial metabolites as signaling bridges.Therapeutically, these insights support the integration of hormone replacement therapy with microbiota-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Such combined strategies may synergistically enhance neuroprotection, though their efficacy depends on timing, dosage, and individual variability. Future precision approaches integrating multi-omics profiling and sex-specific stratification hold promise for identifying predictive biomarkers and optimizing treatment windows. In summary, the EGMB axis offers a mechanistic foundation for understanding sex differences in AD and a translational framework for developing individualized, multidimensional strategies for early diagnosis, prevention, and therapy.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Progress and Perspectives on the Estrogen–Microbiota–Brain Axis in Alzheimer’s Disease

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief