The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Items 401–500 of 1,000
Liu, J., Zhen, D., Hu, C., Liu, Y., Shen, X., Fu, P., & He, Y. (2022) · Nutrients · doi:10.3390/nu14173635 · Cited by 24
“Evtepia_gabavorous can lead to anxiety, depression, and restlessness by reducing the neurotransmitter GABA (γ-aminobutyric acid) [63].”
BackgroundSelf-citationRafiq, T., Stearns, J. C., Shanmuganathan, M., Azab, S. M., Anand, S. S., Thabane, L., Beyene, J., Williams, N. C., Morrison, K. M., Teo, K. K., et al. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e16651 · Cited by 24
Microbiome‐skin‐brain axis: A novel paradigm for cutaneous wounds
Hadian, Y., Fregoso, D. R., Nguyen, C., Bagood, M. D., Dahle, S. E., Gareau, M. G., & Isseroff, R. R. (2020) · Wound Repair and Regeneration · doi:10.1111/wrr.12800 · Cited by 26
Cheng, J., Wu, Q., Sun, R., Li, W., Wang, Z., Zhou, M., Tian, Y., Wang, J., Lyu, Y., & Yue, C. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1438928 · Cited by 25
“(Mazzoli et al., 2016; Strandwitz et al., 2019).”
Action and immunomodulatory mechanisms, formulations, and safety concerns of probiotics
Ashaolu, T. J., Greff, B., & Varga, L. (2024) · Bioscience of Microbiota Food and Health · doi:10.12938/bmfh.2024-006 · Cited by 26
Guo, Z., Xiao, S., Chen, G., Zhong, S., Zhong, H., Sun, S., Chen, P., Tang, X., Yang, H., Jia, Y., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03207-0 · Cited by 26
Braga, J. D., Yang, Y., Nagao, T., Katô, N., Yanaka, N., Nishio, K., Okada, M., Kuroda, M., Yamaguchi, S., & Kumrungsee, T. (2025) · npj Science of Food · doi:10.1038/s41538-025-00383-1 · Cited by 23
“Eubacterium has been reported to be both a GABA producer and consumer 44 .”
Enzymatic Reactions Involving Ketyls: From a Chemical Curiosity to a General Biochemical Mechanism
Buckel, W. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00171 · Cited by 24
Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines
Guo, Y., Bian, X., Liu, J., Zhu, M. Q., Li, L., Yao, T., Tang, C., Ravichandran, V., Liao, P., Papadimitriou, K., et al. (2020) · Foods · doi:10.3390/foods9081045 · Cited by 23
“In addition, in the mouse tumor model, inulin diet intervention was found to increase the relative abundance of many intestinal bacteria with anti-tumor potential, such as Bifidobacterium, Bacteroides, Parabacteroides, Akkermansia muciniphila, and Barnesiella, further showing restrictions on the growth of colon cancer…”
BackgroundSelf-citationBoulaka, A., Christodoulou, P., Vlassopoulou, M., Koutrotsios, G., Bekiaris, G., Zervakis, G. I., Mitsou, E. K., Saxami, G., Kyriacou, A., Zervoú, M., et al. (2020) · Molecules · doi:10.3390/molecules25153554 · Cited by 23
“Recent in vitro and in vivo data demonstrated that the abundance of GABA-producing bacteria is correlated with brain neuronal activity influencing the host [54] and disorder in GABA signalling is implicated in a multitude of neurologic and psychiatric conditions [55].”
BackgroundMárquez-Morales, L., El-Kassis, E. G., Cavazos‐Arroyo, J., Rocha–Rocha, V. M., Martínez‐Gutiérrez, F., & Pérez‐Armendáriz, B. (2021) · Nutrients · doi:10.3390/nu13051551 · Cited by 29
“Previous studies have shown that the genera Lactobacillus and Bifidobacteria, belonging to the phyla Firmicutes and Actinobacteria, respectively, are producers of gamma-aminobutiric acid and serotonin [16], both of which are altered in stressed individuals [17], causing dysbiosis characterized by the growth of enterob…”
ResultLynch, C. M. K., Nagpal, J. K., Clarke, G. A., & Cryan, J. F. (2021) · Current Opinion in Physiology · doi:10.1016/j.cophys.2021.100468 · Cited by 25
Zhang, S., Qian, Y., Li, Q., Xu, X., Li, X., Wang, C., Cai, H., Zhu, J., & Yu, Y. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.750704 · Cited by 24
“…connectivity between core reward regions in patients with obesity after laparoscopic sleeve gastrectomy (Dong et al., 2020) and lower connectivity between the dorsolateral prefrontal cortex and anterior medial frontal cortex in patients with major depressive disorder (Strandwitz et al., 2019).”
BackgroundHammond, T. C., Green, S. J., Jacobs, Y., Chlipala, G. E., Xing, X., Heil, S. D., Chen, A., Aware, C. B., Flemister, A., Stromberg, A. J., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1227203 · Cited by 24
“The relative abundance of bacteria from the genus, part of the Bacteroidetes phylum and related to altered dopamine signaling through its synthetization of GABA (Strandwitz et al., 2019; Kramer et al., 2020), were negatively correlated with CBF in the basal ganglia regions and hippocampal regions, both implicated in l…”
InfluentialLiu, X., van Beek, N., Čepić, A., Andreani, N. A., Chung, C. J., Hermes, B. M., Yilmaz, K., Benoit, S., Drenovska, K., Gerdes, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1212551 · Cited by 22
“GABA shunt is a pathway involving the conversion of L-glutamate into GABA, and next converting GABA into succinate with the presence of a -Ketoglutaric acid, which is then coupled with the tricarboxylic acid cycle (46).”
BackgroundGut production of GABA by a probiotic formula: an in vitro study
Casertano, M., Fryganas, C., Valentino, V., Troise, A. D., Vitaglione, P., Fogliano, V., & Ercolini, D. (2017) · Beneficial Microbes · doi:10.1163/18762891-20230025 · Cited by 23
He, W., Zhang, S., Qi, Z., & Liu, W. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107201 · Cited by 23
Jia, X., Chen, Q., Zhang, Y., & Asakawa, T. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1296713 · Cited by 22
Fernández-Cantos, M. V., Babu, A. F., Hanhineva, K., & Kuipers, O. P. (2024) · Microbiological Research · doi:10.1016/j.micres.2024.127700 · Cited by 22
Gao, M., Chen, S., Fan, H., Li, P., Liu, A., Li, D., Li, X., Hu, Y., Han, G., Guo, Y., et al. (2025) · iMeta · doi:10.1002/imt2.70044 · Cited by 22
“During the fetal stage, the primary bacteria responsible for GABA production are Escherichia coli , Bacteroides , and Bifidobacterium [42].”
Pharmacology of GABA and Its Receptors
Kaur, S., Singh, S., Arora, A., Ram, P., Kumar, S., Kumar, P., & Abed, S. N. (2020) · Springer eBooks · doi:10.1007/978-981-15-3556-7_8 · Cited by 23
Bai, M., Liu, H., Wang, S., Shu, Q., Xu, K., Zhou, J. W., Xiong, X., Huang, R., Deng, J., Yin, Y., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.679129 · Cited by 22
“Bacteroides and Parabacteroides, occurring in the early stages of life, have been reported to produce gamma amino butyric acid, associated with growth (53).”
BackgroundDecoding the Role of Gut-Microbiome in the Food Addiction Paradigm
Novelle, M. G. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18136825 · Cited by 24
Ding, Y., Ou, Y., Yan, H., Fu, X., Yan, M., Li, H., Liu, F., & Guo, W. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.833592 · Cited by 22
Wang, H., Liu, J., He, J., Huang, D., Xi, Y., Xiao, T., Ouyang, Q., Zhang, S., Wan, S., & Chen, X. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1063489 · Cited by 24
“GABA antagonists were found to reverse depression-like behaviors, and increased GABA activity could improve depression status (49).”
BackgroundSelf-citationGreen, J. E., McGuinness, A. J., Berk, M., Castle, D. J., Athan, E., Hair, C., Strandwitz, P., Loughman, A., Nierenberg, A. A., Cryan, J. F., et al. (2023) · Pilot and Feasibility Studies · doi:10.1186/s40814-023-01235-z · Cited by 23
“Conversely, faecal microbiota transplant (FMT), which encompasses a complete human gut microbiome containing thousands of potentially symbiotic strains [17], may have the potential to more effectively alter the composition of the gut microbiota, thus the influence of FMT on mental health symptoms warrants further expl…”
BackgroundSelf-citationPhage Interactions with the Nervous System in Health and Disease
Jędrusiak, A., Fortuna, W., Majewska, J., Górski, A., & Jończyk‐Matysiak, E. (2023) · Cells · doi:10.3390/cells12131720 · Cited by 25
“produce γ-aminobutyric acid (GABA) [104], which is the main inhibitory neurotransmitter in the human cortex [108].”
BackgroundXie, Y., Wu, Z., Qian, Q., Yang, H., Ma, J., Luan, W., Shang, S., & Li, X. (2024) · Food & Function · doi:10.1039/d3fo04606k · Cited by 22
The Microbiome and Its Potential for Pharmacology
Chavira, A., Belda‐Ferre, P., Kościółek, T., Ali, F., Dorrestein, P. C., & Knight, R. D. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_317 · Cited by 21
Self-citationAdvanced Bioinspired Multifunctional Platforms Focusing on Gut Microbiota Regulation
Li, M., Wang, L., Lin, D., Liu, Z., Wang, H., Yang, Y., Sun, C., Ye, J., & Liu, Y. (2024) · ACS Nano · doi:10.1021/acsnano.4c05013 · Cited by 24
Li, S., Liu, M., Han, Y., Liu, C., Cao, S., Cui, Y., Zhu, X., Wang, Z., Liu, B., & Shi, Y. (2024) · mSystems · doi:10.1128/msystems.01015-24 · Cited by 24
“It has been reported that g__Bacteroides can produce GABA to mediate the regulation of bodily functions (31).”
BackgroundLi, J., Zhao, J., Ze, X., Li, L., Li, Y., Zhou, Z., Wu, S., Jia, W., Liu, M., Li, Y., et al. (2024) · Food & Function · doi:10.1039/d4fo01684j · Cited by 24
The effect of exercise on depression and gut microbiota: Possible mechanisms
Yao, M., Qu, Y., Zheng, Y., & Guo, H. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.111130 · Cited by 26
Xu, M., Li, W., Hu, X., & Zhang, J. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c11643 · Cited by 22
Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder
Zhou, Q., Sun, T., Wu, F., Li, F., Liu, Y., Li, W., Dai, N., Tan, L., Li, T., & Song, Y. (2020) · Journal of Traditional Chinese Medical Sciences · doi:10.1016/j.jtcms.2020.10.005 · Cited by 22
Decoding the Genomic Variability among Members of the Bifidobacterium dentium Species
Lugli, G. A., Tarracchini, C., Alessandri, G., Milani, C., Mancabelli, L., Turroni, F., Bunešová, V., Ruíz, L., Margollés, A., & Ventura, M. (2020) · Microorganisms · doi:10.3390/microorganisms8111720 · Cited by 21
“Another intriguing characteristic of this bifidobacterial species is the ability to produce γ-aminobutyric acid (GABA), which is a neuroactive molecule involved in the modulation of neural signals that affect neurological and psychiatric parameters as well as sleep, appetite, mood, and cognition [32,33].”
Backgroundde Bie, T. H., Balvers, M. G. J., de Vos, R. C. H., Witkamp, R. F., & Jongsma, M. A. (2022) · Food & Function · doi:10.1039/d2fo01358d · Cited by 21
Differences in uterine and serum metabolome associated with metritis in dairy cows
Figueiredo, C. C., Balzano‐Nogueira, L., Bisinotto, D. Z., Ruiz, A. R., Duarte, G. A., Conesa, A., Galvão, K. N., & Bisinotto, R. S. (2023) · Journal of Dairy Science · doi:10.3168/jds.2022-22552 · Cited by 21
“Although the role of GABA in the uterus is not clear, it was reported that approximately 90% of Bacteroides genomes harbor the glutamic acid decarboxylase system for GABA production in the human gut (Strandwitz et al., 2019).”
Getting closer to modeling the gut-brain axis using induced pluripotent stem cells
Hall, V. J., & Bendtsen, K. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1146062 · Cited by 21
“These include a wide range of GM-produced neuromodulators, such as serotonin (Enteroccoccus, Escherichia etc.) (Yano et al., 2015), γaminobutyric/GABA (Bifidobacterium, Lactobacillus) (Strandwitz et al., 2019), and acethylcholine (Lactobacillus) (Nimgampalle and Kuna, 2017).”
Bendriss, G., MacDonald, R. S., & McVeigh, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511978 · Cited by 25
Contribution of the seminal microbiome to paternal programming
Kilama, J., Dahlen, C. R., Reynolds, L. P., & Amat, S. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae068 · Cited by 23
Xia, T., Huang, F., Yun, F., Liu, Y., Wang, T., Wang, S., Jin, S., Ma, X., Wang, W., He, J., et al. (2024) · Current Research in Food Science · doi:10.1016/j.crfs.2024.100924 · Cited by 22
Firoozi, D., Masoumi, S. J., Asl, S. M. K. H., Fararouei, M., & Jamshidi, S. (2025) · Journal of Nutrition and Metabolism · doi:10.1155/jnme/3165876 · Cited by 23
“Additionally, the microbiota of the gut produces neurotransmitters such as dopamine, γ -aminobutyric acid (GABA), and serotonin, which impact mood [10–12].”
Recent advances in the application of microbiota transplantation in chickens
Zhao, H., Comer, L., Akram, M. Z., Corion, M., Li, Y., & Everaert, N. (2025) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-025-01233-6 · Cited by 20
Role of the gut microbiome in Alzheimer’s disease
Chok, K. C., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0122 · Cited by 22
Liu, L., Zou, Z., Yang, J., Li, X., Zhu, B., Zhang, H., Sun, Y., Zhang, Y., Zhang, Z., & Wang, W. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.645638 · Cited by 21
Bishop, S. L., Drikic, M., Wacker, S., Chen, Y. Y., Kozyrskyj, A. L., & Lewis, I. A. (2022) · Mucosal Immunology · doi:10.1038/s41385-022-00553-4 · Cited by 19
Zhang, K., Liu, G., Wu, Y., Zhang, T., Guo, M., Yu, L., Cao, X., Suo, L., Brügger, D., Wang, X., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.02955-22 · Cited by 23
“In addition, certain commensal bacteria in the gut create the precursor neurotransmitter 5-HT as well as neurotransmitters, including dopamine, g -aminobutyric acid, and norepinephrine (38).”
BackgroundThe role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases
Wu, N., Li, X., Ma, H., Zhang, X., Liu, B., Yuan, W., Zheng, Q., & Fan, X. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1108738 · Cited by 22
“In the immune system, the GABAergic signaling system plays a key role in response to various inflammatory disorders and influences various functional properties of the immune cells, such as LPS-induced cytokine release, antigen-induced T-cells proliferation, cytotoxicity and chemotaxis of effector T-cells activity (70…”
BackgroundInfluentialTolpežnikaitė, E., Bartkevičs, V., Skrastina, A., Pavlenko, R., Ružauskas, M., Starkutė, V., Zokaitytė, E., Klupšaitė, D., Ruibys, R., Rocha, J. M., et al. (2023) · Biology · doi:10.3390/biology12020248 · Cited by 22
Toward understanding links between the microbiome and neurotransmitters
Lynch, J. B., & Hsiao, E. Y. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14993 · Cited by 22
Tanihiro, R., Yuki, M., Sasai, M., Haseda, A., Kagami‐Katsuyama, H., Hirota, T., Honma, N., & Nishihira, J. (2023) · Nutrients · doi:10.3390/nu16010141 · Cited by 21
“Hence, Bacteroides were suggested to be the main GABA-producing bacteria in the human large intestine [56].”
BackgroundAlteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection
Sun, M., Chen, H., Dong, S., Zhang, G., Zhou, X., & Cheng, H. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106458 · Cited by 20
“A definitive link between a lack of Bacteroides and depression has been reported (Strandwitz et al., 2019).”
BackgroundGut microbiota composition links to variation in functional domains across psychiatric disorders
Mulder, D., Jakobi, B., Shi, Y., Mulders, P. C. R., Kist, J. D., Collard, R. M., Vrijsen, J. N., van Eijndhoven, P., Tendolkar, I., Bloemendaal, M., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.05.037 · Cited by 20
Gut microbiota metabolites: potential therapeutic targets for Alzheimer’s disease?
Zhang, S., Lu, J., Jin, Z., Xu, H., Zhang, D., Chen, J., & Wang, J. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1459655 · Cited by 25
“This fi nding has been corroborated by human fecal transcriptome analysis (Chang et al., 2020; Strandwitz et al., 2019).”
BackgroundChoi, B. S.-Y., Daoust, L., Pilon, G., Marette, A., & Tremblay, A. (2020) · International Journal of Obesity · doi:10.1038/s41366-020-0618-3 · Cited by 20
Bacteria-immune cells dialog and the homeostasis of the systems
Guzman-Bautista, E. R., Suzuki, K., Asami, S., & Fagarasan, S. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.05.010 · Cited by 21
Zhu, L., Mack, C., Wirtz, A., Kranz, A., Polen, T., Baumgart, M., & Bott, M. H. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.544045 · Cited by 20
The gut microbiome and adult hippocampal neurogenesis: A new focal point for epilepsy?
Dohm-Hansen, S., Donoso, F., Lucassen, P. J., Clarke, G. A., & Nolan, Y. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105746 · Cited by 21
Marzouk, N. H., Rashwan, H. H., El-Hadidi, M. S., Ramadan, R., & Mysara, M. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00950-z · Cited by 21
“Tech.) andtype used,theaccessionnumberfor thedataincluded. producing GABA from the collection reported in the work of Strandwitz et al. 16 .”
InfluentialArbutin ameliorated depression by inhibiting neuroinflammation and modulating intestinal flora
Cao, Y., Zhao, K., Zhao, Y., Ni, Y., Zhang, Z., Yuan, X., Ning, J., Song, Q., Zhao, F., He, L., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156944 · Cited by 21
Mottawea, W., Sultan, S., Landau, K., Bordenave, N., & Hammami, R. (2020) · Nutrients · doi:10.3390/nu12092669 · Cited by 21
“Considering the putative mechanisms of action of psycho-biotics, such food products or preliminary formulations could be screened ex vivo for their ability to increase microbiota diversity, increase microbial production of bioactive metabolites such as SCFA, neurotransmitters GABA, serotonin and dopamine, and for thei…”
BackgroundInfluentialOluwagbemigun, K., Schnermann, M. E., Schmid, M. C., Cryan, J. F., & Nöthlings, U. (2022) · Gut Pathogens · doi:10.1186/s13099-022-00487-z · Cited by 20
“Further, Pseudomonas is one of the gamma aminobutyric acid-modifying genera [41] and gamma aminobutyric acid level is lower in individuals with Alzheimer’s disease as compared to healthy individuals, [42].”
BackgroundGut–Brain Axis, Neurodegeneration and Mental Health: A Personalized Medicine Perspective
Chunduri, A., Reddy, S. D. M., Jahanavi, M., & Reddy, C. N. (2022) · Indian Journal of Microbiology · doi:10.1007/s12088-022-01033-w · Cited by 22
“Depression and low mood conditions have been linked with the downregulation of tryptophan metabolism [25].”
BackgroundMo, L., Jing, H., Du, X., Zhao, C., Lin, Y., Li, J., & Wang, H. (2023) · Food & Function · doi:10.1039/d3fo00797a · Cited by 21
Gao, Y., Liang, Z., Mao, B., Zheng, X., Shan, J., Jin, C., Liu, S., Kolliputi, N., Chen, Y., Xu, F., et al. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.06.008 · Cited by 20
“Recent studies exhibit that some species of intestinal bacteria, such as Lactobacillus, Bacteroides, Parabacteroides, and Escherichia, could modulate GABA metabolism and influence the pathophysiology of the nervous system or other proximal or distal tissues [11,12].”
BackgroundWang, Q., Zhao, Y.-X., Qin, X., & Tian, J. (2024) · Chinese Herbal Medicines · doi:10.1016/j.chmed.2023.12.003 · Cited by 19
“These findings show that the gut microbiota is involved in the arginine metabolism pathway in depressed patients (Strandwitz et al., 2019).”
Along the microbiota–gut–brain axis: Use of plant polysaccharides to improve mental disorders
Gao, J., Liang, Y., & Liu, P. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130903 · Cited by 21
Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice
Bokoliya, S. C., Russell, J. T., Dorsett, Y., Panier, H. A., Singh, V., Daddi, L., Yuan, H., Dedon, L. R., Liu, Z., Zhou, Y., et al. (2024) · Microbiome · doi:10.1186/s40168-024-01829-6 · Cited by 18
“Previous studies have identified a variety of GABA-producers and degraders in the gut microbiome [60, 61].”
BackgroundAssociations of Microbiota and Nutrition with Cognitive Impairment in Diseases
Młynarska, E., Jakubowska, P., Frąk, W., Gajewska, A., Sornowska, J., Skwira, S., Wasiak, J., Rysz, J., & Franczyk, B. (2024) · Nutrients · doi:10.3390/nu16203570 · Cited by 19
“GABA, an inhibitory neurotransmitter, was shown to be produced by certain bacteria species in the gut, such as Parabacteroides, Eubacterium , and Bifidobacterium , and act locally in the intestine [73,74].”
BackgroundPetersen, A. Ø., Jokinen, M., Plichta, D. R., Liebisch, G., Gronwald, W., Dettmer, K., Oefner, P. J., Vlamakis, H. C., Chung, D. C., Ranki, A., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.03.025 · Cited by 20
Bedi, S., Richardson, T. M., Jia, B., Saab, H., Brinkman, F. S. L., & Westley, M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0261103 · Cited by 22
“Healthy individuals have a greater gut bacterial diversity with GABA-producing pathways activated in several bacterial species compared to T1D donor stool samples [22].”
BackgroundEvidence-Based Analysis of Neurotransmitter Modulation by Gut Microbiota
Liu, T., & Huang, Z. (2019) · Lecture notes in computer science · doi:10.1007/978-3-030-32962-4_22 · Cited by 20
HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis
Hu, A., Zaongo, S. D., Harypursat, V., Wang, X., Ouyang, J., & Chen, Y. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1428239 · Cited by 18
Huang, R., Zhang, J., Sun, M., Xu, L., Kuang, H., Xu, C., & Guo, L. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.141129 · Cited by 20
Puetz, L., Delmont, T. O., Aizpurua, O., Guo, C., Zhang, G., Katajamaa, R., Jensen, P., & Gilbert, M. T. P. (2021) · Advanced Genetics · doi:10.1002/ggn2.202100018 · Cited by 18
Smythe, P., & Efthimiou, G. (2022) · Microorganisms · doi:10.3390/microorganisms10071341 · Cited by 18
“While propionate is the second-most abundant SCFA produced by L. reuteri F275, L. reuteri DSM 20016 is a lab culture of F275, which may have undergone genomic changes due to lab cultivation.”
BackgroundInfluentialLebovich, M., & Andrews, L. B. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.938056 · Cited by 17
“The metabolite gamma-aminobutyric acid (GABA) is a human neurotransmitter produced by some bacteria found in the gut (Strandwitz et al., 2019) and has been shown to affect mood and sleep disorders (Sigel and Steinmann 2012; Diez-Gutiérrez et al.”
BackgroundGut Microbiota Host–Gene Interaction
Cuomo, P., Capparelli, R., Alifano, M., Iannelli, A., & Iannelli, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213717 · Cited by 19
“Deficit of GABA is associated with depressive symptoms [19].”
Backgroundde Llano, D. G., Roldán, M., Parro, L., Bartolomé, B., & Moreno-Arribas, M. V. (2023) · Metabolites · doi:10.3390/metabo13010108 · Cited by 19
“Concerning indirect signaling, the microbial metabolism affects the regulation of the neuroendocrine system [12] and the production of neurotransmitters [13].”
BackgroundUnderstanding the ADHD-Gut Axis by Metabolic Network Analysis
Taş, E., & Ülgen, K. Ö. (2023) · Metabolites · doi:10.3390/metabo13050592 · Cited by 18
“L-Glutamate GABA Lactobacillus, Bifidobacterium, Bacteroides, Parabacteroides, Escherichia [32,33]”
Characteristic Gut Bacteria in High Barley Consuming Japanese Individuals without Hypertension
Maruyama, S., Matsuoka, T., Hosomi, K., Park, J., Nishimura, M., Murakami, H., Konishi, K., Miyachi, M., Kawashima, H., Mizuguchi, K., et al. (2023) · Microorganisms · doi:10.3390/microorganisms11051246 · Cited by 19
“Additionally, although γ-aminobutyric acid (GABA) is known to be one of the beneficial metabolites of intestinal bacteria that is well-known to prevent hypertension, bacteria belonging to Bacteroides, Parabacteroides, and Escherichia, which have been reported to belong to GABA-producing genera [59], showed no differen…”
BackgroundThe Role of the Microbiome in First Episode of Psychosis
Nuncio-Mora, L., Lanzagorta, N., Nicolini, H., Sarmiento, E., Ortiz, G., Sosa, F., & Mendoza, A. D. G. (2023) · Biomedicines · doi:10.3390/biomedicines11061770 · Cited by 18
“This is important because alterations in central GABA receptor expression are implicated in depression and anxiety.”
BackgroundInfluentialA review of the auditory-gut-brain axis
Graham, A. S., Ben‐Azu, B., Tremblay, M., Torre, P., Senekal, M., Laughton, B., van der Kouwe, A. J. W., Jankiewicz, M., Kaba, M., & Holmes, M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1183694 · Cited by 22
“Various studies in animals and humans have identified the vagus nerve, hypothalamic–pituitary–adrenal (HPA) axis, the immune system, neurotransmitters and bacterial metabolites as probable regulators of gut-brain axis signaling (Ait-Belgnaoui et al., 2012; Iven et al., 2019; Lin et al., 2019; Strandwitz et al., 2019;…”
BackgroundNovel therapeutic strategies in glioma targeting glutamatergic neurotransmission
Kumaria, A., & Ashkan, K. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148515 · Cited by 20
Culturing the unculturables: strategies, challenges, and opportunities for gut microbiome study
Yadav, A., Ahlawat, S., & Sharma, K. K. (2023) · Journal of Applied Microbiology · doi:10.1093/jambio/lxad280 · Cited by 18
A Review on the Protective Effects of Probiotics against Alzheimer’s Disease
Mishra, V., Yadav, D., Solanki, K. S., Koul, B., & Song, M. (2023) · Biology · doi:10.3390/biology13010008 · Cited by 20
“Lactobacillus , Streptococcus , and Escherichia coli generate 5-HT in the gut [83].”
BackgroundLonstein, J. S., Meinhardt, T. A., Pavlidi, P., Kokras, N., Dalla, C., Charlier, T. D., & Pawluski, J. L. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107033 · Cited by 18
Gastrodin ameliorates depressive-like behaviors via modulating gut microbiota in CUMS-induced mice
Zhao, Y., Qin, S.-K., Yang, Z., Lu, Y. F., Ma, Z., Xin, P., Sun, G., & Pei, L. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.114968 · Cited by 18
“These gut microbes can produce high neuroactive potential of metabolites such as dopamine, noradrenaline, serotonin and GABA and other neurotrans-mitters that play a role in regulating mood [65,68].”
Tao, W., Zhang, Y., Wang, B., Nie, S., Li, F., Xiao, J., & Wu, Y. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.03.023 · Cited by 21
“Moreover, as an essential growth factor, GABA induces the growth of GM, thereby regulating the GM structure under stress condition [66,72].”
InfluentialXie, Y., Shang, S., Luan, W., Ma, J., Yang, H., Qian, Q., Wu, Z., & Li, X. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c07035 · Cited by 18
Chen, K., Sun, L., Liu, Y., & Chen, R. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1639911 · Cited by 20
Microbial Metabolomes in Alzheimer’s Disease: From Pathogenesis to Therapeutic Potential
Borrego-Ruiz, A., & Borrego, J. J. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090724 · Cited by 21
“Emerging evidence suggests that GABA is also synthesized by the GM, with key contributions from genera such as Alistipes , Bacteroides , Bifidobacterium , Blautia , Escherichia , Lacticigenium , and Lactobacillus [119,120,197].”
Li, X., Jing, K., Lu, H., Li, K., Zhang, Y., & Hasichaolu, H. (2022) · BioMed Research International · doi:10.1155/2022/6334868 · Cited by 16
“In summary, we speculate that Bacteroides barnesiae may modulate human mental health through the production of GABA and thus act as a key neuroimmune modulator.”
InfluentialLiu, S., Wen, B., Du, G., Wang, Y., Ma, X., Yu, H., Zhang, J., Fan, S., Zhou, H., & Xin, F. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.134436 · Cited by 18
Topic modeling for multi-omic integration in the human gut microbiome and implications for Autism
Tataru, C. A., Peras, M., Rutherford, E. M., Dunlap, K., Yin, X., Chrisman, B., DeSantis, T. Z., Wall, D. P., Iwai, S., & David, M. M. (2023) · Scientific Reports · doi:10.1038/s41598-023-38228-0 · Cited by 17
Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis
Caspani, G., Ruffell, S., Tsang, W., Netzband, N., Rohani-Shukla, C., Swann, J. R., & Jefferies, W. A. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107338 · Cited by 18
“Similarly, a negative relationship exists between faecal Bacteroides and the functional connectivity between the left dorsolateral prefrontal cortex (dlPFC) and the DMN in major depression [173].”
A review on gut microbiota and miRNA crosstalk: implications for Alzheimer’s disease
Ayyanar, M. P., & Vijayan, M. (2024) · GeroScience · doi:10.1007/s11357-024-01432-5 · Cited by 22
Impact of Fermented Milk On Gut Microbiota And Human Health: A Comprehensive Review
EL‐SALAM, M. H. A., El‐Shibiny, S., Assem, F. M., El-Sayyad, G. S., Hasanien, Y. A., Elfadil, D., & Soliman, T. N. (2025) · Current Microbiology · doi:10.1007/s00284-025-04061-z · Cited by 18
“Low counts of faecal Bacteroides as γ-aminobutyric acid (GABA) were found to be producing bacteria in patients with major depression disorder, which suggests the importance of GABA to normal brain function [145].”
Cheng, Y., Zhu, Z., Yang, Z., Liu, X., Qian, X., Zhu, J., Hu, X., Jiang, P., Cui, T., Wang, Y., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-97369-6 · Cited by 21
“Strandwitz et al. found an inverse relationship between Bacteroides and brain activity patterns related to depression 62 .”
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
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
