The balance of microbial species making up the gut microbiome changes with age in ways that (a) promote chronic inflammation, such as via infiltration of microbes into tissue and production of harmful metabolites, and (b) reduce the supply of beneficial metabolites, such as butyrate. A growing body of work characterizes these changes and links them to specific age-related conditions. A number of studies have demonstrated that common neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease, correlate with distinct dysfunctional changes in the aging gut microbiome.
Today's open access paper adds to this body of work, and in addition to assessing cognitive function and composition of the gut microbiome also incorporates a measure of brain biological age derived from imaging of brain tissue. All three of these measures tend to move with one another; those people with greater dysbiosis of the gut microbiome also have an older brain age and greater loss of cognitive function. One might hypothesize that either the changes in the gut microbiome are contributing to neurodegeneration, or that immune aging contributes to all of the above. Or both!
There is a bidirectional relationship between the state of the aging immune system and the state of the aging gut microbiome. On the one hand the immune system gardens the gut microbiome, removing problem microbes. As the immune system falters with age, it becomes less able to conduct this duty. On the other hand, changes in the composition of the gut microbiome can affect the immune system both directly, by provoking chronic inflammation, and indirectly, via metabolites and other signaling that affects the state of tissues and organs needed for immune function, such as bone marrow and the thymus.
Brain age mediates gut microbiome dysbiosis-related cognition in older adults
The human gut microbiome, a complex and dynamic ecosystem of microorganisms, plays a vital role in maintaining host health and influencing disease progression. Central to this understanding is the concept of the "gut-brain axis," a bidirectional communication network linking the enteric and central nervous systems (CNS) through neural, endocrine, immune, and humoral pathways. Through these mechanisms, the gut microbiome has been hypothesized to affect brain development, behavior, and cognitive function.
Emerging research suggests that gut microbiome dysbiosis - a state of microbial imbalance - is associated with accelerated gray matter aging. Dysbiosis has been linked to inflammation and increased intestinal permeability, leading to systemic and neural inflammation that can negatively impact cognitive function. Aging appears to exacerbate these changes, marked by decreased diversity in beneficial microbial species, such as anti-inflammatory Bifidobacterium, and increased prevalence of pro-inflammatory species like Enterococcus. These microbial shifts, coupled with reduced immunological function and heightened release of inflammatory products, may further accelerate brain aging, contribute to cognitive decline, and even promote amyloid and tau deposition associated with Alzheimer's disease.
We recruited 292 participants from South Korean memory clinics to undergo brain magnetic resonance imaging, clinical assessments, and collected stool samples. We employed a pretrained brain age model derived from imaging data - a measure associated with neurodegeneration. Using cluster analysis, we categorized individuals based on their microbiome profiles and examined the correlations with brain age, Mental State Examination (MMSE) scores, and the Clinical Dementia Rating Sum of Box (CDR-SB).
Two clusters were identified in the microbiota at the phylum level that showed significant differences on a few microbiotas phylum. Greater gut microbiome dysbiosis was associated with worse cognitive function including MMSE and CDR-SB; this effect was partially mediated by greater brain age even when accounting for chronological age, sex, and education. Our findings indicate that brain age mediates the link between gut microbiome dysbiosis and cognitive performance. These insights suggest potential interventions targeting the gut microbiome to alleviate age-related cognitive decline.
View the full article at FightAging
