Mechanistic Interplay of Gut Microbiota and Blood-Brain Barrier Integrity in Neurodegenerative Diseases

Mohammad SI 1 , Hammood YM 2 , Vasudevan A 3 , Uthirapathy S 4 , Ballal S 5 , Sabarivani A 6 Show all authors , Mishra S 7 , Nathiya D 8 , Al-Qaim ZH 9 , Kadhim AJ 10

Affiliations 

  • 1 Electronic Marketing and Social Media, Economic and Administrative Sciences, Zarqa University, Zarqa, Jordan
  • 2 College of Physical Education and Sport Science, Al-Maarif University, Anbar, Iraq. yasiralmohana@uoa.edu.iq
  • 3 Faculty of Business and Communications, INTI International University, 71800, Negeri Sembilan, Malaysia
  • 4 Pharmacy Department, Tishk International University, Erbil, Kurdistan Region, Iraq
  • 5 Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
  • 6 Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
  • 7 Department of Pharmacology, IMS and SUM Hospital, Siksha O Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
  • 8 Department of Pharmacy Practice, NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
  • 9 Anesthesia Techniques Department, College of Health and Medical Techniques, Al-Mustaqbal University, Babylon, Iraq
  • 10 Department of Medical Engineering, Al-Nisour University College, Baghdad, Iraq
Mol Neurobiol, 2025 Nov 22;63(1):137.
PMID: 41273600 DOI: 10.1007/s12035-025-05447-7

Abstract

The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining overall health through digestion, nutrient production, and immune modulation. Factors such as diet, lifestyle, and medication use significantly influence its composition. Concurrently, the blood-brain barrier (BBB) serves as a crucial protective barrier, regulating the passage of substances between the bloodstream and the brain. Disruption of the BBB is linked to various neurological disorders and cognitive decline. Neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's, can be exacerbated by compromised BBB integrity, allowing harmful substances to penetrate the brain and accelerate neuronal degeneration. This review examines the complicated relationship between gut microbiota and BBB integrity, focusing on their collective impact on neurodegenerative diseases. Despite advancements in understanding these systems independently, there remains a critical gap in comprehending their interconnected roles in neurodegeneration. Addressing this gap is paramount for developing innovative therapeutic strategies. Specifically, this review suggests that modulating the gut microbiota offers a promising and actionable approach to preserve BBB integrity, thereby presenting a novel avenue for mitigating neurodegeneration and improving the prognosis and quality of life for affected individuals.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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