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Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Age-dependent effects of gut microbiota metabolites on brain resident macrophages
Dilara Hasavci1, Thomas Blank1
1Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
Abstract:
In recent years, development of age-related diseases, such as Alzheimer's and Parkinson's disease, as well as other brain disorders, including anxiety, depression, and schizophrenia have been shown to be associated with changes in the gut microbiome. Several factors can induce an alteration in the bacterial composition of the host's gastrointestinal tract. Besides dietary changes and frequent use of antibiotics, the microbiome is also profoundly affected by aging. Levels of microbiota-derived metabolites are elevated in older individuals with age-associated diseases and cognitive defects compared to younger, healthy age groups. The identified metabolites with higher concentration in aged hosts, which include choline and trimethylamine, are known risk factors for age-related diseases. While the underlying mechanisms and pathways remain elusive for the most part, it has been shown, that these metabolites are able to trigger the innate immunity in the central nervous system by influencing development and activation status of brain-resident macrophages. The macrophages residing in the brain comprise parenchymal microglia and non-parenchymal macrophages located in the perivascular spaces, meninges, and the choroid plexus. In this review, we highlight the impact of age on the composition of the microbiome and microbiota-derived metabolites and their influence on age-associated diseases caused by dysfunctional brain-resident macrophages.
Insights
Aging alters the gut microbiome, increasing metabolites linked to brain disorders like Alzheimer's. These changes impact brain immune cells, contributing to age-related cognitive decline and diseases.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Age-related diseases (Alzheimer's, Parkinson's) and brain disorders are linked to gut microbiome changes.
- Aging significantly impacts gut bacterial composition and microbiota-derived metabolites.
- Elevated metabolites like choline and trimethylamine in older adults correlate with cognitive defects.
Purpose of the Study:
- To review the impact of aging on gut microbiome composition and metabolites.
- To explore the influence of these metabolites on age-associated brain diseases.
- To highlight the role of dysfunctional brain-resident macrophages.
Main Methods:
- Literature review focusing on aging, gut microbiome, metabolites, and neuroinflammation.
- Analysis of studies linking microbiota-derived metabolites to age-related cognitive function.
- Examination of the role of brain-resident macrophages (microglia and others) in disease pathogenesis.
Main Results:
- Aging alters the gut microbiome, leading to increased levels of specific metabolites.
- Metabolites such as choline and trimethylamine are risk factors for age-related diseases.
- These metabolites can activate innate immunity in the central nervous system via brain macrophages.
Conclusions:
- Dysfunctional brain-resident macrophages, influenced by aging-related microbiome changes, contribute to age-associated brain disorders.
- Understanding these mechanisms is crucial for developing therapeutic strategies.
- Further research is needed to elucidate the precise pathways involved.
