Gut microbiota, an additional hallmark of human aging and neurodegeneration

Gut microbiota represents a diverse and dynamic population of microorganisms harbouring the gastrointestinal tract, which influences host health and disease. Bacterial colonization of the gastrointestinal tract begins at birth and changes throughout life, with age being one of the conditioning factors for its vitality. Aging is also a primary risk factor for most neurodegenerative diseases. Among them, Alzheimeŕs disease (AD) is probably the one where its association with a state of dysbiosis of the gut microbiota has been most studied. In particular, intestinal microbial-derived metabolites have been associated with β-amyloid formation and brain amyloid deposition, tau phosphorylation, as well as neuroinflammation in AD patients. Moreover, it has been suggested that some oral bacteria increase the risk of developing AD. However, the causal connections among microbiome, amyloid-tau interaction, and neurodegeneration need to be addressed. This paper summarizes the emerging evidence in the literature regarding the link between the oral and gut microbiome and neurodegeneration with a focus on AD. Taxonomic features of bacteria as well as microbial functional alterations associated with AD biomarkers are the main points reviewed. Data from clinical studies as well as the link between microbiome and clinical determinants of AD are particularly emphasized. Further, relationships between gut microbiota and age-dependent epigenetic changes and other neurological disorders are also described. Together, all this evidence suggests that, in some sense, gut microbiota can be seen as an additional hallmark of human aging and neurodegeneration.

Funding: Research in our labs is funded by Grants PID2019-108851RB-C21, PGC2018-096177-B-I00 & PID2021-123859OB-100 (Spanish Ministry of Science and Innovation), and ALIBIRD-CM 2020 P2018/BAA-4343 (Comunidad de Madrid, Spain). The authors would like to thank CSIC Interdisciplinary Thematic Platform (PTI + NEURO-AGING+) and Institutional grants from the Fundación Ramón Areces and Banco de Santander are also acknowledged.

Peer reviewed