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Published on: July 27, 2022
GABA-modulating bacteria of the human gut microbiota
Philip Strandwitz1, Ki Hyun Kim2,3, Darya Terekhova4
1Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA. p.strandwitz@northeastern.edu.
The gut bacterium KLE1738 requires gamma-aminobutyric acid (GABA) for growth, a neurotransmitter produced by Bacteroides species. Gut Bacteroides abundance correlates with brain activity in major depressive disorder patients.
Area of Science:
- Microbiology and Neuroscience
- Gut Microbiota and Host Physiology
Background:
- The human gut microbiota plays a crucial role in host functions, including immune and nervous system regulation.
- A significant portion of gut microbial species remain uncultured, hindering the understanding of their biological roles.
- Unculturability is often attributed to the lack of essential growth factors present in the in situ environment.
Purpose of the Study:
- To identify essential growth factors for uncultured gut bacteria.
- To investigate the role of neurotransmitters in microbial growth and metabolism.
- To explore the link between gut microbiota composition, GABA production, and major depressive disorder.
Main Methods:
- Co-culturing techniques were employed to isolate the uncultured bacterium KLE1738.
- Bioassay-guided purification identified gamma-aminobutyric acid (GABA) as a key growth factor for KLE1738.
- Genome analysis, metabolic modeling, transcriptome analysis of human stool, and functional MRI in patients were utilized.
Main Results:
- Gamma-aminobutyric acid (GABA) was identified as the sole nutrient supporting the growth of the uncultured gut bacterium KLE1738.
- Bacteroides species were found to be significant producers of GABA, with multiple other genera capable of producing or consuming it.
- Active expression of GABA-producing pathways was observed in Bacteroides, Parabacteroides, and Escherichia species in healthy individuals.
- A negative correlation was found between fecal Bacteroides abundance and brain signatures associated with major depressive disorder.
Conclusions:
- Gamma-aminobutyric acid (GABA) is a critical growth factor for certain uncultured gut bacteria, linking neurotransmitter metabolism to microbial ecology.
- The gut microbiota, particularly Bacteroides species, actively produces GABA, influencing the gut-brain axis.
- Alterations in gut Bacteroides abundance may be associated with neurological conditions like major depressive disorder via GABA-mediated pathways.
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