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Updated: Jul 4, 2025
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Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
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Abnormalities in microbiota/butyrate/FFAR3 signaling in aging gut impair brain function.
Sidharth P Mishra1,2,3, Shalini Jain1,2,3, Bo Wang4
1USF Center for Microbiome Research.
JCI Insight
|February 8, 2024
Summary
Aging gut microbiota causes inflammation and cognitive decline by reducing butyrate. Restoring butyrate levels can improve gut and brain health in older adults.
Area of Science:
- Microbiology
- Neuroscience
- Gastroenterology
Background:
- Aging alters gut microbiota composition, linked to cognitive and mood disorders.
- Mechanisms connecting aged gut microbiota to brain dysfunction are poorly understood.
Purpose of the Study:
- To investigate the causal link between aged gut microbiota and gut-brain axis abnormalities.
- To identify the role of butyrate and its receptors in age-related cognitive and mood deficits.
Main Methods:
- Fecal microbiota transplantation from aged to young mice.
- Assessment of gut barrier integrity, inflammation markers, and cognitive/anxiety behaviors.
- Analysis of butyrate levels, mucin production, and free fatty acid receptor 2/3 (FFAR2/3) expression.
- Intervention with butyrate and genetic manipulation of FFAR2/3.
Main Results:
- Old microbiota transplantation induced gut inflammation, leaky gut, and cognitive/anxiety issues in young mice.
- Reduced butyrate production and FFAR2/3 signaling were observed in aged microbiota.
- Butyrate administration reversed inflammation and brain dysfunction.
- Intestine-specific FFAR2/3 loss mimicked age-related gut-brain abnormalities.
Conclusions:
- Reduced butyrate and FFAR2/3 signaling in aged gut microbiota drive gut barrier dysfunction and brain abnormalities.
- Targeting butyrate-FFAR2/3 pathways offers a therapeutic strategy for age-related gut-brain axis decline.
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