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GABA-modulating bacteria of the human gut microbiota
Open accessAbstract
The gut microbiota affects many important host functions, including the immune response and the nervous system1. However, while substantial progress has been made in growing diverse microorganisms of the microbiota2, 23–65% of species residing in the human gut remain uncultured3,4, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ5,6. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression. A bacterial strain that requires the neurotransmitter GABA for growth was identified and used to isolate GABA-producing bacteria, including Bacteroides spp., from human stool samples; the relative abundance of Bacteroides was negatively correlated with an altered GABA-mediated response in a depression patient cohort.
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“Studies have shown that gut microbiota is capable of producing or stimulating the production of neurotransmitters, including serotonin,33–35 dopamine,36 and γ-aminobutyric acid (GABA).37”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [37]
In the citing paper
“The GM can metabolize GABA and recent research has shown that certain microbes can produce GABA, required for their growth (235).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [235]
In the citing paper
“Furthermore, abundances of faecal GABA-producers, such as Bacteroides, correlate negatively with brain signatures associated with depression [77].”
From Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse (2020) · cites this paper as [77]
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Hu, B., Das, P., Lv, X., Shi, M., Aa, J., Wang, K., Duan, L., Gilbert, J. A., Nie, Y., & Wu, X. (2021) · Research Square · doi:10.21203/rs.3.rs-917357/v2
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Assistance of Gut Microbiota in Depression
Reji, R. T., Krishna, R., & Kumar, R. S. (2021) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v11i6-s.5202
“By coupling 16S ribosomal RNA sequencing with functional magnetic resonance imaging in patients with major depressive disorder, the researchers found out that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression [44].”
BackgroundProbiotics Composition Harbors Against Osteoarthritis and Inflammation through GABA in MicePreprint
Amin, U., Jiang, R., Raza, S. M., Li, L., Feng, N., Yang, Y., & Guo, F. (2022) · Research Square · doi:10.21203/rs.3.rs-1206549/v1
Gut microbiota – invaluable guardian of immunity and vitality of the human body
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“Dobrym przykładem jest tu zdolność do produkcji neuroprzekaźnika znanego jako GABA – kwasu gammaaminomasłowego – przez bakterie z rodzaju Bacteroides, Bifidobacterium, Parabacteroides oraz Escherichia [31].”
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The gut microbiome as a therapeutic target in systemic disease
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Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infectionPreprint
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Gut microbiota characteristics in children with cerebral palsy
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Research Progress of Intestinal Flora and Related Diseases
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Vitamin B6, Magnesium, and Vitamin D: The Triple Play
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“Gut microbiome studies of both LC [28] and CFS [29] report deficiencies in butyrate and GABA producing bacteria, e.g., Bacteroides [30], Bifidobacterium dentium [31], and Lactobacillus brevium [32]. triggers Bacteroides not only drives gut microbiota diversity but also is one of only six known…”
Background
Metadata
- Authors
- Strandwitz, P., Kim, K. H., Terekhova, D., Liu, J. K., Sharma, A., Levering, J., McDonald, D., Dietrich, D., Ramadhar, T. R., Lekbua, A., Mroue, N., Liston, C., Stewart, E. J., Dubin, M. J., Zengler, K., Knight, R., Gilbert, J. A., Clardy, J., & Lewis, K.
- Affiliations
- Northeastern University (US)
- Harvard University (US)
- Weill Cornell Medicine (US)
- University of California San Diego (US)
- Argonne National Laboratory (US)
- Corresponding author
- Strandwitz, Philip
- Lewis, Kim
- ORCID
- Venue
- Nature Microbiology
- Published
- 2018-12-10
- Volume
- 4
- Issue
- 3
- Pages
- 396-403
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC6384127
- OpenAlex
- W2902161130
- Semantic Scholar
- e557d4ef36b36019dcd3ba0973119440d4426bca
- Cited by
- 1,170
- References
- 55
- Citations by year
- 2026: 153 · 2025: 187 · 2024: 225 · 2023: 176 · 2022: 141 · 2021: 131 · 2020: 110 · 2019: 46
- FWCI
- 26.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- Faculty of Arts and Sciences
- National Human Genome Research Institute (R01HG005824)
- National Institute of General Medical Sciences (F32GM108415)
- National Institute of Allergy and Infectious Diseases (R01AI122286)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Agricultural and Biological Sciences › Plant Science › GABA and Rice Research
- Keywords
- GABA, gut microbiota, Bacteroides, GABA-producing bacteria, bacterial growth factors, co-culture, Bacteroides fragilis, Parabacteroides, Escherichia, major depressive disorder, functional MRI, neurotransmitter metabolism, uncultured bacteria
- MeSH terms
- Gastrointestinal Microbiome, Whole Genome Sequencing, Adult, Aged, Bacteria, Bacteroides, Brain, Depression, Depressive Disorder, Major, Major Depressive Disorder, Feces, Female, gamma-Aminobutyric Acid, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Cohort Studies, Gene Expression Profiling, Gastrointestinal Tract, Young Adult
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