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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Gut microbiota is capable of producing or stimulating the production of neurotransmitters, including serotonin, dopamine, and γ-aminobutyric acid (GABA).
“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]
The GM can metabolize GABA, and certain microbes produce GABA required for their growth.
“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]
Abundances of faecal GABA-producers, such as Bacteroides, correlate negatively with brain signatures associated with depression.
“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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The future of rodent models in depression research
Gururajan, A., Reif, A., Cryan, J. F., & Slattery, D. A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0221-6 · Cited by 269 · see citing works
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“16 Another possible underlying pathway is through the immune system, based on the evidence that the abnormal brain immune signals and exacerbated peripheral inflammation reactions have been detected in many neuropsychiatric disorders.”
Kong, C., Liang, L., Liu, G., Du, L., Yang, Y., Liu, J., Shi, D., Li, X., & Ma, Y. (2023) · Gut · doi:10.1136/gutjnl-2022-327156 · Cited by 254 · see citing works
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The gut microbiota–brain axis in neurological disorder
Ullah, H., Arbab, S., Tian, Y., Liu, C., Chen, Y., Li, Q., Khan, M. I. U., Hassan, I. U., & Li, K. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1225875 · Cited by 279 · see citing works
“These neuroactive metabolites, such as the neurotransmitters GABA, dopamine, noradrenaline and serotonin, amino acids (for example, tryptophan and tyramine) T lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), long-chain fatty acids (LCFAs), trimethylamine-N-oxide (TAMO), and polysaccharide A (PSA), either dir…”
BackgroundInfluentialDiez-Gutiérrez, L., Vicente, L. S., Barrón, L. J. R., Villarán, M. C., & Chávarri, M. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103669 · Cited by 257 · see citing works
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Microbiota Metabolites in Health and Disease
McCarville, J. L., Chen, G. Y., Cuevas, V. D., Troha, K., & Ayres, J. S. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-071219-125715 · Cited by 251 · see citing works
Gut microbiome composition and diversity are related to human personality traits
Johnson, K. V. ‐. (2019) · Human Microbiome Journal · doi:10.1016/j.humic.2019.100069 · Cited by 241 · see citing works
“More recently it has been reported that the relative abundance of Bacteroides is negatively associated with brain signatures of depression [28], suggesting that bacterially derived GABA may play a role in the microbiome–gut–brain axis.”
BackgroundZhuang, Z., Yang, R., Wang, W., Qi, L., & Huang, T. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01961-8 · Cited by 220 · see citing works
Gamma-aminobutyric acid as a potential postbiotic mediator in the gut–brain axis
Braga, J. D., Thongngam, M., & Kumrungsee, T. (2024) · npj Science of Food · doi:10.1038/s41538-024-00253-2 · Cited by 240 · see citing works
“GABA-producing microorganisms isolated from the human gut Several gastrointestinal (GI) bacteria contain the gene encoding GAD 36,37 , which is responsible for GABA production (Table 1).”
BackgroundInfluentialLi, Z., Lai, J., Zhang, P., Ding, J., Jiang, J., Liu, C., Huang, H., Zhen, H., Xi, C., Sun, Y., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01569-9 · Cited by 226 · see citing works
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Personalized whole‐body models integrate metabolism, physiology, and the gut microbiome
Thiele, I., Sahoo, S., Heinken, A., Hertel, J., Heirendt, L., Aurich, M. K., & Fleming, R. M. T. (2020) · Molecular Systems Biology · doi:10.15252/msb.20198982 · Cited by 215 · see citing works
Tănase, D. M., Gosav, E. M., Neculae, E., Costea, C. F., Ciocoiu, M., Hurjui, L. L., Tărniceriu, C. C., Maranducă, M. A., Lăcătușu, C.-M., Floria, M., et al. (2020) · Nutrients · doi:10.3390/nu12123719 · Cited by 209 · see citing works
“The interaction between the microbiota and the host is still not fully understood, but there are a few studied mechanisms through which the microbiota produces different molecules such as SCFAs, neuro-hormones or mimetics (GABA and Caseinolytic protease B) and imidazole propionate [44,102].”
BackgroundMicrobial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
“This molecule was recently shown to be both a product of bacteria in the gut [250, 253, 254] and an important substrate for other gut community members [255].”
BackgroundEnlightening the taxonomy darkness of human gut microbiomes with a cultured biobank
Liu, C., Du, M., Abuduaini, R., Yu, H., Li, D., Wang, Y., Zhou, N., Jiang, M.-Z., Niu, P.-X., Han, S.-S., et al. (2021) · Microbiome · doi:10.1186/s40168-021-01064-3 · Cited by 205 · see citing works
“Furthermore, previous works showed that cultivated gut microbial resources played fundamental roles not only in culture-dependent causative studies of host-GM interactions [17-19] but also in the cultivation-independent omics studies [20-22].”
BackgroundAntidepressive Mechanisms of Probiotics and Their Therapeutic Potential
Yong, S. J., Tong, T., Chew, J., & Lim, W. L. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01361 · Cited by 217 · see citing works
Cohen, L. J., Cho, J. H., Gevers, D., & Chu, H. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.017 · Cited by 201 · see citing works
Pathology of pain and its implications for therapeutic interventions
Cao, B., Xu, Q., Shi, Y., Zhao, R., Li, H., Zheng, J., Liu, F., Wan, Y., & Wei, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01845-w · Cited by 220 · see citing works
When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis
Teichman, E. M., O’Riordan, K. J., Gahan, C. G. M., Dinan, T. G., & Cryan, J. F. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.02.008 · Cited by 198 · see citing works
Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism
Miro-Blanch, J., & Yanes, O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00638 · Cited by 195 · see citing works
“In the same direction, Thaiss et al. (2016) used a combination of metagenomics, transcriptomics, epigenomics, and metabolomics together with imaging electron microscopy, to identify a diurnal rhythmicity in the microbial biogeography, metabolic profile, and metagenomic functionality as critical…”
Gut microbiota bridges dietary nutrients and host immunity
Fan, L., Xia, Y., Wang, Y., Han, D., Liu, Y., Li, J., Fu, J., Wang, L., Gan, Z., Liu, B., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2346-1 · Cited by 197 · see citing works
“, 2019), and there exists a crosstalk between GABA and intestinal microbiota (Strandwitz et al., 2019); nevertheless, whether and how gut microbiota med-”
BackgroundToro-Barbosa, M. D., Hurtado‐Romero, A., García-Amezquita, L. E., & García‐Cayuela, T. (2020) · Nutrients · doi:10.3390/nu12123896 · Cited by 195 · see citing works
“Lastly, a transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides [41].”
BackgroundBeneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota
Yu, L., Han, X. J., Cen, S., Duan, H., Feng, S., Xue, Y., Tian, F., Zhao, J., Zhang, H., Zhai, Q., et al. (2020) · Microbiological Research · doi:10.1016/j.micres.2020.126409 · Cited by 185 · see citing works
Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease
Zhu, M., Liu, X., Ye, Y., Yan, X., Cheng, Y., Zhao, L., Chen, F., & Ling, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.937555 · Cited by 177 · see citing works
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The gut microbiota and mental health in adults
Järbrink‐Sehgal, E., & Andréasson, A. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.01.016 · Cited by 176 · see citing works
Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome?
Miri, S., Yeo, J., Abubaker, S., & Hammami, R. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1098412 · Cited by 167 · see citing works
“The relative abundance of Bacteroides was negatively correlated with depression-associated brain signatures (Strandwitz et al., 2019), indicating a significant role of microbiome-secreted GABA in brain functionality.”
BackgroundInfluentialBacterial Metabolites of Human Gut Microbiota Correlating with Depression
Averina, O. V., Zorkina, Y., Yunes, R. А., Kovtun, A. S., Ushakova, V. M., Morozova, A. Y., Kostyuk, G. P., Даниленко, В. Н., & Chekhonin, V. P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239234 · Cited by 166 · see citing works
“According to a post-mortem study, the levels of reduced, oxidized, and total GSH are significantly lower in the PFC of MDD patients [106].”
BackgroundInfluentialZhu, R., Fang, Y., Li, H., Liu, Y., Wei, J., Zhang, S., Wang, L., Fan, R., Wang, L., Li, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1158137 · Cited by 166 · see citing works
Chen, M., Ruan, G., Chen, L., Ying, S., Li, G., Xu, F., Xiao, Z., Tian, Y., Lv, L., Ping, Y., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.817100 · Cited by 159 · see citing works
“fragilis KLE1758 (42) Pregabalin, gabapentin or”
Toward Understanding Microbiome-Neuronal Signaling
Jameson, K. G., Olson, C. A., Kazmi, S. A., & Hsiao, E. Y. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.006 · Cited by 150 · see citing works
Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption
Rothenberg, D. O., & Zhang, L. (2019) · Nutrients · doi:10.3390/nu11061361 · Cited by 147 · see citing works
“Tea polyphenols have shown variable effects on Bacteroides, another potentially psychobiotic species whose abundance was shown to negatively correlate with brain signatures associated with depression [157].”
BackgroundHenriques, S. F., Dhakan, D. B., Serra, L., Francisco, A. P., Carvalho-Santos, Z., Baltazar, C., Elias, A. P., Anjos, M., Zhang, T., Maddocks, O. D. K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18049-9 · Cited by 146 · see citing works
Microbiota‐gut‐brain axis as a regulator of reward processes
García‐Cabrerizo, R., Carbia, C., O’Riordan, K. J., Schellekens, H., & Cryan, J. F. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15284 · Cited by 147 · see citing works
Zhang, W., Qu, W., Wang, H., & Yan, H. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01254-5 · Cited by 152 · see citing works
Sophisticated natural products as antibiotics
Lewis, K., Lee, R. E., Jr., Brötz‐Oesterhelt, H., Hiller, S., Rodnina, M. V., Schneider, T., Weingarth, M. H., & Wohlgemuth, I. (2024) · Nature · doi:10.1038/s41586-024-07530-w · Cited by 144 · see citing works
“The two tryptophan rings appear to be conserved in most analogues, whereas other residues on the 7-mer peptide are variable 10 .”
Self-citationSleep Disturbance as Potential Risk and Progression Factor for Parkinson’s Disease
Bohnen, N. I., & Hu, M. T. M. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191627 · Cited by 144 · see citing works
“If enteric synucleinopathy and/or change in the gut microbiome may be one of the earliest events in some patients with PD, then the observations of GABA producing/consuming bacteria in the gut [54], and evidence of vagal nerve mediated GABA-ergic influences on the brain may have the potential to disrupt the delicate G…”
BackgroundHorvath, T. D., Ihekweazu, F. D., Haidacher, S. J., Ruan, W. H., Engevik, K. A., Fultz, R., Hoch, K. M., Luna, R. A., Oezguen, N., Spinler, J. K., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104158 · Cited by 142 · see citing works
Gao, M., Wang, J., Liu, P., Tu, H., Zhang, R., Zhang, Y., Sun, N., & Zhang, K. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02670-5 · Cited by 149 · see citing works
The Gut and Parkinson's Disease—A Bidirectional Pathway
Santos, S. F., de Oliveira, H. L., Yamada, E. S., Neves, B. C., & Pereira, A. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00574 · Cited by 144 · see citing works
Artificial cells drive neural differentiation
Toparlak, Ö. D., Zasso, J., Bridi, S., Serra, M. D., Macchi, P., Conti, L., Baudet, M., & Mansy, S. S. (2020) · Science Advances · doi:10.1126/sciadv.abb4920 · Cited by 140 · see citing works
“A genetically programmable system that is similar to what was described here could be envisaged to integrate within the gut-brain axis by exploiting the naturally occurring quorum signaling pathways between bacteria ( 31 , 32 ).”
Mhanna, A., Martini, N., Hmaydoosh, G., Hamwi, G., Jarjanazi, M., Zaifah, G., Kazzazo, R., Mohamad, A. H., & Alshehabi, Z. (2024) · Medicine · doi:10.1097/md.0000000000037114 · Cited by 144 · see citing works
“[37] The Parabacteroides and Eubacterium genera were identified as GABA producers, [38] along with Lactobacillus, Bifidobacterium, Bacteroides , [37] and Blautia , [39] specifically Bacteroides fragilis .”
BackgroundProbiotics synergized with conventional regimen in managing Parkinson’s disease
Sun, H., Zhao, F., Liu, Y., Ma, T., Jin, H., Quan, K., Leng, B., Zhao, J., Yuan, X., Li, Z., et al. (2022) · npj Parkinson's Disease · doi:10.1038/s41531-022-00327-6 · Cited by 136 · see citing works
Benítez‐Páez, A., Kjølbæk, L., del Pulgar, E. M. G., Brahe, L. K., Astrup, A. V., Matysik, S., Schött, H.-F., Krautbauer, S., Liebisch, G., Boberska, J., et al. (2019) · mSystems · doi:10.1128/msystems.00209-19 · Cited by 136 · see citing works
“rium species, also have been described to be GABA-producing gut microbes (46, 47).”
BackgroundThe role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
Fujii, Y., Nguyen, T. T. T., Fujimura, Y., Kameya, N., Nakamura, S., Arakawa, K., & Morita, H. (2019) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2019.1644149 · Cited by 133 · see citing works
Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy
Lin, B., Wang, Y., Zhang, P., Yuan, Y., Zhang, Y., & Chen, G. (2020) · The Journal of Headache and Pain · doi:10.1186/s10194-020-01170-x · Cited by 131 · see citing works
microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data
Zuffa, S., Schmid, R., Bauermeister, A., Gomes, P. W. P., Caraballo‐Rodríguez, A. M., Abiead, Y. E., Aron, A. T., Gentry, E. C., Zemlin, J., Meehan, M. J., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-023-01575-9 · Cited by 125 · see citing works
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · see citing works
Reduced anti-inflammatory gut microbiota are associated with depression and anhedonia
Mason, B. L., Li, Q., Minhajuddin, A., Czysz, A. H., Coughlin, L. A., Hussain, S. K., Koh, A. Y., & Trivedi, M. H. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.137 · Cited by 127 · see citing works
Addolorato, G., Ponziani, F. R., Dionisi, T., Mosoni, C., Vassallo, G. A., Sestito, L., Petito, V., Picca, A., Marzetti, E., Tarli, C., et al. (2020) · Liver International · doi:10.1111/liv.14383 · Cited by 125 · see citing works
van de Wouw, M., Walsh, A. M., Crispie, F., van Leuven, L., Lyte, J. M., Boehme, M., Clarke, G., Dinan, T. G., Cotter, P. D., & Cryan, J. F. (2020) · Microbiome · doi:10.1186/s40168-020-00846-5 · Cited by 123 · see citing works
Ortega, M. A., Álvarez-Mon, M. Á., Montero, C. G., Fraile‐Μartinez, O., Guijarro, L. G., Lahera, G., Monserrat, J., Valls, P., Mora, F., Rodríguez–Jiménez, R., et al. (2022) · Metabolites · doi:10.3390/metabo12010050 · Cited by 125 · see citing works
“Besides, Bacteroides Parabacteroides and Escherichia species are also importantly involved in the synthesis of GABA, with a negative correlation between fecal Bacteroides and brain signatures associated with depression [140].”
BackgroundGut microbiome-mediated regulation of neuroinflammation
Bostick, J. W., Schonhoff, A. M., & Mazmanian, S. K. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102177 · Cited by 118 · see citing works
γ-Aminobutyric acid found in fermented foods and beverages: current trends
Sahab, N. R. M., Subroto, E., Balia, R. L., & Utama, G. L. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e05526 · Cited by 117 · see citing works
The Gut-Brain Axis: Two Ways Signaling in Parkinson’s Disease
Dogra, N., Mani, R. J., & Katare, D. P. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01066-7 · Cited by 117 · see citing works
The receptor hypothesis and the pathogenesis of depression: Genetic bases and biological correlates
Wang, H., Wang, Z., & Chen, N. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105542 · Cited by 117 · see citing works
Gut microbiota and bone metabolism
Lu, L., Chen, X., Liu, Y., & Yu, X. (2021) · The FASEB Journal · doi:10.1096/fj.202100451r · Cited by 120 · see citing works
Szopinska-Tokov, J., Dam, S. A., Naaijen, J., Konstanti, P., Rommelse, N., Belzer, C., Buitelaar, J., Franke, B., Bloemendaal, M., Aarts, E., et al. (2020) · Microorganisms · doi:10.3390/microorganisms8030406 · Cited by 100 · see citing works
“gabavorous seems to be the only isolated human gut bacteria showing ability to consume gamma aminobutyric acid (GABA) [52,53].”
BackgroundInfluentialManipulating exudate composition from root apices shapes the microbiome throughout the root system
Kawasaki, A., Dennis, P. G., Forstner, C., Raghavendra, A., Mathesius, U., Richardson, A. E., Delhaize, E., Gilliham, M., Watt, M., & Ryan, P. R. (2021) · PLANT PHYSIOLOGY · doi:10.1093/plphys/kiab337 · Cited by 113 · see citing works
Farag, M. A., Abdelwareth, A., Sallam, I. E., Shorbagi, M., Jehmlich, N., Fritz‐Wallace, K., Schäpe, S. S., Rolle-Kampczyk, U. E., Ehrlich, A., Wessjohann, L. A., et al. (2020) · Journal of Advanced Research · doi:10.1016/j.jare.2020.01.001 · Cited by 112 · see citing works
“GABA can also be utilized by bacteria as carbon source through conversion to succinate which enters the tricarboxylic acid cycle [78] and this may explain the coexistence of GABA and succinic acid (r2 = 0.”
BackgroundMicrobiota-brain interactions: Moving toward mechanisms in model organisms
Nagpal, J. K., & Cryan, J. F. (2021) · Neuron · doi:10.1016/j.neuron.2021.09.036 · Cited by 107 · see citing works
Tette, F.-M., Kwofie, S. K., & Wilson, M. D. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44040096 · Cited by 114 · see citing works
Genetic and metabolic links between the murine microbiome and memory
Mao, J., Kim, Y., Zhou, Y., Hu, D., Zhong, C., Chang, H., Brislawn, C., Fansler, S. J., Langley, S. A., Wang, Y., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00817-w · Cited by 108 · see citing works
“Increased levels of GABA in the brain could also be due to increased production of GABA by gut bacteria [15, 16].”
BackgroundHu, B., Das, P., Lv, X., Shi, M., Aa, J., Wang, K., Duan, L., Gilbert, J. A., Nie, Y., & Wu, X. (2022) · mSystems · doi:10.1128/msystems.00218-22 · Cited by 107 · see citing works
Self-citationGut Microbiota Interaction with the Central Nervous System throughout Life
Ojeda, J., Ávila, A., & Vidal, P. M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10061299 · Cited by 107 · see citing works
“In humans, Bacteroides ssp, Parabacteroides, and Escherichia species are GABA producers required for neighboring bacteria, including Pseudomonas, Acinetobacter, and Mycobacterium genera [45].”
BackgroundDilmore, A. H., Martino, C., Neth, B. J., West, K., Zemlin, J., Rahman, G., Panitchpakdi, M. W., Meehan, M. J., Weldon, K. C., Blach, C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13007 · Cited by 104 · see citing works
“45 This led us to re-investigate the relative relationship between Akkermansia muciniphila and Alistipes sp. CAG:514 and levels of the GABA metabolite in our population.”
BackgroundSelf-citationForte, N. R., Fernández-Rilo, A. C., Palomba, L., Marzo, V. D., & Cristino, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051554 · Cited by 104 · see citing works
“GABA Both host and bacteria have the capacity to convert the amino acid glutamate to GABA [94,95], the major inhibitory neurotransmitter of the host nervous system.”
BackgroundInfluentialFu, J., Li, J., Sun, Y., Liu, S., Song, F., & Liu, Z. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.123488 · Cited by 103 · see citing works
Emerging targetome and signalome landscape of gut microbial metabolites
Zheng, X., Cai, X., & Hao, H. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.011 · Cited by 100 · see citing works
Averina, O. V., Kovtun, A. S., Polyakova, S. I., Savilova, A. M., Rebrikov, D. V., & Даниленко, В. Н. (2020) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001178 · Cited by 103 · see citing works
Conn, K. A., Borsom, E. M., & Cope, E. K. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2371950 · Cited by 105 · see citing works
“30,169 As discussed above, the composition of the gut micro-biome is altered in AD, and Bacteroides is frequently identified as differentially abundant in disease.”
BackgroundGut microbiota alterations reveal potential gut–brain axis changes in polycystic ovary syndrome
Liang, Z., Di, N., Li, L., & Yang, D. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01481-5 · Cited by 109 · see citing works
“For the first time, we found increasing GABA-producing species in PCOS, with Parabacteroides distasonis increased in both PCOS and lean PCOS against controls and Bacteroides fragilis as well as Escherichia coli increased in PCOS against controls [40].”
BackgroundGuo, Y., Zhu, X., Zeng, M., Qi, L., Tang, X., Wang, D., Zhang, M., Xie, Y., Li, H., Yang, X., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01443-2 · Cited by 104 · see citing works
Exploitation of microbial activities at low pH to enhance planetary health
Atasoy, M., Álvarez‐Ordóñez, A., Cenian, A., Djukić‐Vuković, A., Lund, P. A., Özoğul, F., Trček, J., Ziv, C., & Biase, D. D. (2023) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuad062 · Cited by 110 · see citing works
“…acid), a metabolite associated with several physiological functions in humans, such as strengthening of blood vessels, insulin secretion modulation, increased blood c holester ol pr e v ention, or mitigation of emotional unr est, among others (Rashmi et al. 2018 , Strandwitz et al. 2018 ).”
Background
- 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 · 2017: 1
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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