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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]
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“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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Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
Self-citationHamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies
Stamatakis, A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu033 · Cited by 32,291
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
Prodigal: prokaryotic gene recognition and translation initiation site identification
Hyatt, D., Chen, G.-L., LoCascio, P. F., Land, M., Larimer, F. W., & Hauser, L. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-119 · Cited by 12,692
The RAST Server: Rapid Annotations using Subsystems Technology
Aziz, R. K., Bartels, D., Best, A. A., DeJongh, M., Disz, T. L., Edwards, R. A., Formsma, K., Gerdes, S., Glass, E. M., Kubal, M., et al. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-75 · Cited by 11,893
Haas, B. J., Papanicolaou, A., Yassour, M., Grabherr, M., Blood, P. D., Bowden, J., Couger, M. B., Eccles, D., Li, B., Lieber, M., et al. (2013) · Nature Protocols · doi:10.1038/nprot.2013.084 · Cited by 8,464
Functional connectivity in the resting brain: a network analysis of the default mode hypothesis
Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0135058100 · Cited by 6,358
UniProt: a hub for protein information
The UniProt Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku989 · Cited by 5,106
Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888
Research works printed but not linked: 1
- Sneath, P. H. Principles of bacterial taxonomy. Proc. R. Soc. Med. 65, 851–852 (1972).
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
The gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Chen, Y., Xu, J., & Chen, Y. (2021) · Nutrients · doi:10.3390/nu13062099 · Cited by 917
“Besides short-chain fatty acids and bile acids, recent studies show that the metabolites produced by the gut microbiota also include some neurotransmitters such as glutamate, GABA, serotonin, and dopamine [19,29,32].”
BackgroundInfluentialFord, A. C., Mahadeva, S., Carbone, F., Lacy, B. E., & Talley, N. J. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30469-4 · Cited by 587
McGuinness, A. J., Davis, J. A., Dawson, S. L., Loughman, A., Collier, F., O’Hely, M., Simpson, C. A., Green, J., Marx, W., Hair, C., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01456-3 · Cited by 502
Gut Bacteria and Neurotransmitters
Dicks, L. M. T. (2022) · Microorganisms · doi:10.3390/microorganisms10091838 · Cited by 482
“More recently, a new “GABA-eating” species, Evtepia gabavorous within the family Ruminococcaceae, has been described [115,117].”
BackgroundMicrobiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462
“The human microbiome harbors a variety of microbial species capable of producing neurotransmitters, signaling molecules, or metabolizing their precursors into distinct compounds.(145,189,201) As certain bacterium may contribute significantly to the levels of gut-derived metabolites observed in the host,(138) it is com…”
BackgroundSignalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415
Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders
Yang, J., Zheng, P., Li, Y., Wu, J., Tan, X., Zhou, J., Sun, Z., Chen, X., Zhang, G., Zhang, H., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba8555 · Cited by 411
“In line with our assumption, a previous study has shown that microbial-derived GABA may influence the host through the gut-brain axis (29), and GABA-producing microbes can improve depression-like behavior (30).”
Precision Nutrition and the Microbiome, Part I: Current State of the Science
Mills, S., Stanton, C., Lane, J. A., Smith, G., & Ross, R. P. (2019) · Nutrients · doi:10.3390/nu11040923 · Cited by 426
“More recently, a co-culture experiment revealed that GABA produced by Bacteroides fragilis was essential for the growth of a gut isolate termed KLE1738 which is believed to be an unreported bacterial genus [108].”
BackgroundGut microbiome diversity is associated with sleep physiology in humans
Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., Parikh, E., Lopez, J. V., & Tartar, J. L. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222394 · Cited by 390
Interaction of the microbiota with the human body in health and diseases
Altveş, S., Yıldız, H. K., & Vural, H. C. (2019) · Bioscience of Microbiota Food and Health · doi:10.12938/bmfh.19-023 · Cited by 398
“Some bacteria, such as Lactobacillus and Bifidobacterium, produce gamma-aminobutyric acid (GABA), which is one of the most important transmitters in the central nervous system [83, 84].”
BackgroundGut microbial molecules in behavioural and neurodegenerative conditions
Needham, B. D., Kaddurah-Daouk, R., & Mazmanian, S. K. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00381-0 · Cited by 379
Targeted isolation and cultivation of uncultivated bacteria by reverse genomics
Cross, K. L., Campbell, J. H., Balachandran, M., Campbell, A. G., Cooper, C. J., Griffen, A. L., Heaton, M., Joshi, S. S., Klingeman, D. M., Leys, E. J., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0260-6 · Cited by 380
Kanmani, S., & Koo, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207551 · Cited by 392
“GABA is the prime inhibitory neurotransmitter in the host nervous system that has been produced by host/microbes through the conversion of amino acid glutamate [30].”
BackgroundGut Microbiome in Progressive Multiple Sclerosis
Cox, L. M., Maghzi, A. H., Liu, S., Tankou, S. K., Dhang, F. H., Willocq, V., Song, A., Wasén, C., Tauhid, S., Chu, R., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26084 · Cited by 292
“clear, but it may be related to the microbial production of neurotransmitters.(78,79) Although there is debate on whether bacterial neurotransmitters cross the blood–brain barrier, it has been shown that administering γ-aminobutyric acid (GABA)-producing Lactobacillus reduces anxiety and depression in animal models,(7…”
BackgroundShandilya, S., Kumar, S., Jha, N. K., Kesari, K. K., & Ruokolainen, J. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.09.005 · Cited by 310
“microbiota modulates the concentration of neurotransmitters in host organism [98].”
Gut liver brain axis in diseases: the implications for therapeutic interventions
Yan, M., Man, S., Sun, B., Ma, L., Guo, L., Huang, L., & Gao, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01673-4 · Cited by 314
“GABA-activating GABA receptors exert a depressant effect and alter behavior in the mammalian CNS. 187 GABA-A receptors are the primary inhibitory neurotransmission receptors in the CNS, which means they are involved in the majority of brain physiological processes.”
BackgroundInfluentialMicrobiota succession throughout life from the cradle to the grave
Martino, C., Dilmore, A. H., Burcham, Z. M., Metcalf, J. L., Jeste, D., & Knight, R. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00768-z · Cited by 275
Self-citationThe microbiota-gut-brain axis in sleep disorders
Wang, Z., Wang, Z., Lu, T., Chen, W., Yan, W., Yuan, K., Shi, L., Liu, X., Zhou, X., Shi, J., et al. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101691 · Cited by 302
“Strandwitz et al. isolated a variety of GABA-producing bacteria in human gut microbiota and found that Bacteroides ssp. could produce lots of GABA [67].”
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281
Feeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis
Schneider, E., O’Riordan, K. J., Clarke, G. A., & Cryan, J. F. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01108-6 · Cited by 317
“Both humans and bacteria possess the ability to transform glutamate into GABA, a major inhibitory neurotransmitter in hosts, with species like Escherichia and Lactobacillus being identified as GABA producers 167 .”
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
Han, Y., Wang, B., Gao, H., He, C., Hua, R., Liang, C., Zhang, S., Wang, Y., Xin, S., & Xu, J. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s384949 · Cited by 265
“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
Self-citationYuan, X., Chen, B., Duan, Z., Xia, Z., Ding, Y., Chen, T., Liu, H., Wang, B., Yang, B., Wang, X., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1987779 · Cited by 273
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 292
“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 277
Otaru, N., Ye, K., Mujezinovic, D., Berchtold, L., Constancias, F., Cornejo, F. A., Krzystek, A., de Wouters, T., Braegger, C., Lacroix, C., et al. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.656895 · Cited by 253
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 255
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 257
“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
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 250
“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 227
Zhang, Y., Fan, Q., Hou, Y., Zhang, X., Yin, Z., Cai, X., Wei, W., Wang, J., He, D., Wang, G., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.02.007 · Cited by 226
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 209
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 210
“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
“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 210
“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 222
Cohen, L. J., Cho, J. H., Gevers, D., & Chu, H. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.017 · Cited by 209
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 236
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 199
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
“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 201
“, 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 204
“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
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
Patterson, E., Ryan, P. M., Wiley, N., Carafa, I., Sherwin, E., Moloney, G., Franciosi, E., Mandal, R., Wishart, D. S., Tuohy, K., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-51781-x · Cited by 168
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 189
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 176
“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 171
“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
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 167
“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 155
Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption
Rothenberg, D. O., & Zhang, L. (2019) · Nutrients · doi:10.3390/nu11061361 · Cited by 151
“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 152
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 150
Zhang, W., Qu, W., Wang, H., & Yan, H. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01254-5 · Cited by 155
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 153
“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 146
“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 144
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 164
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 148
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 142
“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
“[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
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 141
“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
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 135
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 137
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 137
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
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 131
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
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
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 131
“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 120
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 130
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 121
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 122
Gut microbiota and bone metabolism
Lu, L., Chen, X., Liu, Y., & Yu, X. (2021) · The FASEB Journal · doi:10.1096/fj.202100451r · Cited by 127
Szopinska-Tokov, J., Dam, S. A., Naaijen, J., Konstanti, P., Rommelse, N. N. J., Belzer, C., Buitelaar, J. K., Franke, B., Bloemendaal, M., Aarts, E., et al. (2020) · Microorganisms · doi:10.3390/microorganisms8030406 · Cited by 117
“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 114
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 116
“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 110
Tette, F.-M., Kwofie, S. K., & Wilson, M. D. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44040096 · Cited by 119
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
“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 116
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 112
“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 108
“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 105
“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 106
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
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 105
Conn, K. A., Borsom, E. M., & Cope, E. K. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2371950 · Cited by 106
“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
“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 105
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 117
“…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
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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