Volume 29, Issue 163, September 2025

The role of gut microbiota in the pathogenesis of Alzheimer’s disease: A review of the literature

Greta Steć^1♦, Agata Brzyska¹, Jan Siemianowski¹, Weronika Kotnis², Magdalena Pawlak¹, Sandra Prolejko², Błażej Gajęcki¹, Justyna Kopala³, Tomasz Kucharski⁴, Weronika Buczek⁵

¹Central Clinical Hospital of Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland
²Medical University of Lodz, Kościuszki 4, 90-419 Lodz, Poland
³University Clinical Hospital No.2 of the Medical University of Lodz, Żeromskiego 113, 90-549 Lodz, Poland
⁴Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland
⁵Pope John Paul II Independent Public Hospital in Zamość, Poland

^♦Corresponding author
Central Clinical Hospital of Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland

ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-beta (Aβ) accumulation, and neuroinflammation. While classical hypotheses—the amyloid cascade, tau protein pathology, and chronic inflammation—have long been the predominant explanations of AD pathogenesis, recent evidence highlights the fundamental role of the gut microbiota in affecting brain health. This review article describes the pathway through which gut dysbiosis contributes to AD by elevated intestinal permeability, systemic inflammation, disruption of the blood–brain barrier (BBB), and altered production of microbial metabolites. Experimental findings indicate that microbial imbalance in animal models and human groups leads to reduced microbial diversity, elevated levels of proinflammatory cytokines, and increased amyloid pathology. Moreover, gut-derived metabolites such as short-chain fatty acids (SCFAs), bile acids, and neurotransmitters regulate microglial function, synaptic health, and Aβ formation. Therapeutic strategies aimed at the restoration of microbiota homeostasis—dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation (FMT)— have been successful in improving cognitive status and reducing neurodegeneration in preclinical models. Causality is still under investigation, but the microbiota-gut-brain axis is a productive area for future AD research and therapy. Further large-scale, long-term studies will be required to explain the mechanisms and to aid in the development of microbiota-based interventions.

Keywords: Alzheimer’s disease; gut microbiota; neuroinflammation; gut-brain axis; blood–brain barrier

Medical Science, 2025, 29, e165ms3654

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DOI: https://doi.org/10.54905/disssi.v29i163.e165ms3654

Published: 16 September 2025