Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report
Open accessAbstract
Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1–5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45–119%), p < 0.001. The effect was found to be mediated by the cytosolic Ca2+ mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models.
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Butyrate stimulates adenosine triphosphate release from astrocytes in a cytosolic Ca2+-dependent manner.
“A recent in vitro study has found that butyrate stimulated adenosine triphosphate release from astrocytes in a cytosolic Ca2+-dependent manner, suggesting a potential neuroprotective mechanism worth further exploration.251”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [251]
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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · cited 1× · see citing works
“SCFA are produced in the colon largely by the bacterial fermentation of dietary fibers and resistant starch [12,13].”
BackgroundMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · see citing works
Role of the gut microbiota in nutrition and health
Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018) · BMJ · doi:10.1136/bmj.k2179 · Cited by 2,375 · see citing works
Glutamate-mediated astrocyte–neuron signalling
Parpura, V., Basarsky, T. A., Liu, F., Jeftinija, K., Jeftinija, S., & Haydon, P. G. (1994) · Nature · doi:10.1038/369744a0 · Cited by 1,737 · see citing works
Verkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678 · see citing works
Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398 · see citing works
Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders
Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00044 · Cited by 1,189 · see citing works
Butyrate: A Double-Edged Sword for Health?
Liu, H., Wang, J., He, T., Becker, S. R., Zhang, G., Li, D., & Ma, X. (2018) · Advances in Nutrition · doi:10.1093/advances/nmx009 · Cited by 1,158 · see citing works
Free Fatty Acid Receptors in Health and Disease
Kimura, I., Ichimura, A., Ohue‐Kitano, R., & Igarashi, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,032 · see citing works
Chen, Y., Xu, J., & Chen, Y. (2021) · Nutrients · doi:10.3390/nu13062099 · Cited by 917 · see citing works
The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
Short chain fatty acids: Microbial metabolites for gut-brain axis signalling
O’Riordan, K. J., Collins, M., Moloney, G. M., Knox, E. G., Aburto, M. R., Fülling, C., Morley, S. J., Clarke, G. A., Schellekens, H., & Cryan, J. F. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111572 · Cited by 742 · see citing works
Mahmoud, S., Gharagozloo, M., Simard, C., & Gris, D. (2019) · Cells · doi:10.3390/cells8020184 · Cited by 698 · see citing works
Astrocyte-derived ATP modulates depressive-like behaviors
Cao, X., Li, L.-P., Wang, Q., Wu, Q., Hu, H.-H., Zhang, M., Fang, Y.-Y., Zhang, J., Li, S.-J., Xiong, W.-C., et al. (2013) · Nature Medicine · doi:10.1038/nm.3162 · Cited by 615 · see citing works
AhR signaling pathways and regulatory functions
Larigot, L., Juricek, L., Dairou, J., & Coumoul, X. (2018) · Biochimie Open · doi:10.1016/j.biopen.2018.05.001 · Cited by 563 · see citing works
Antidepressant-Like Effects of the Histone Deacetylase Inhibitor, Sodium Butyrate, in the Mouse
Schroeder, F. A., Lin, C. L., Crusio, W. E., & Akbarian, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.036 · Cited by 541 · see citing works
Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy
Lupton, J. R. (2004) · Journal of Nutrition · doi:10.1093/jn/134.2.479 · Cited by 343 · see citing works
Large-Scale Calcium Waves Traveling through Astrocytic Networks In Vivo
Kuga, N., Sasaki, T., Takahara, Y., Matsuki, N., & Ikegaya, Y. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5319-10.2011 · Cited by 262 · see citing works
Frankiensztajn, L. M., Elliott, E., & Koren, O. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.12.003 · Cited by 248 · see citing works
Harada, K., Kamiya, T., & Tsuboi, T. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00499 · Cited by 246 · see citing works
Liu, J., Sun, J., Wang, F., Yu, X., Ling, Z., Li, H., Zhang, H., Jin, J., Chen, W., Pang, M., et al. (2015) · BioMed Research International · doi:10.1155/2015/412946 · Cited by 225 · see citing works
Konopelski, P., & Mogilnicka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031222 · Cited by 218 · see citing works
Yamawaki, Y., Yoshioka, N., Nozaki, K., Ito, H., Oda, K., Harada, K., Shirawachi, S., Asano, S., Aizawa, H., Yamawaki, S., et al. (2018) · Brain Research · doi:10.1016/j.brainres.2017.12.004 · Cited by 204 · see citing works
Dalile, B., Vervliet, B., Bergonzelli, G., Verbeke, K., & Van Oudenhove, L. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0732-x · Cited by 201 · see citing works
Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden
Olsson, L. M., Boulund, F., Nilsson, S., Khan, M. T., Gummesson, A., Fagerberg, L., Engstrand, L. G., Perkins, R., Uhlén, M., Bergström, G. M. L., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.03.002 · Cited by 189 · see citing works
Wei, Y. B., Melas, P. A., Wegener, G., Mathe, A. A., & Lavebratt, C. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu032 · Cited by 186 · see citing works
Dash, S., Syed, Y. A., & Khan, M. R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.880544 · Cited by 179 · see citing works
Fatty Acid Signaling Mechanisms in Neural Cells: Fatty Acid Receptors
Falomir‐Lockhart, L. J., Cavazzutti, G. F., Giménez, E., & Toscani, A. M. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00162 · Cited by 162 · see citing works
THE DENSITY OF TISSUES IN AND ABOUT THE HEAD
Barber, T. W., Brockway, J. A., & Higgins, L. S. (1970) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1970.tb05606.x · Cited by 158 · see citing works
Lin, S., Huang, L., Luo, Z.-C., Li, X., Jin, S., Du, Z., Wu, D., Xiong, W., Huang, L., Luo, Z.-Y., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.014 · Cited by 130 · see citing works
The path toward using microbial metabolites as therapies
Descamps, H. C., Herrmann, B. I., Wiredu, D., & Thaiss, C. A. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.05.063 · Cited by 121 · see citing works
Yamawaki, Y., Fuchikami, M., Morinobu, S., Segawa, M., Matsumoto, T., & Yamawaki, S. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.585663 · Cited by 117 · see citing works
Piacentini, R., Puma, D. D. L., Mainardi, M., Lazzarino, G., Tavazzi, B., Arancio, O., & Grassi, C. (2017) · Glia · doi:10.1002/glia.23163 · Cited by 116 · see citing works
Yang, T., Magee, K. L., Colón-Pérez, L. M., Larkin, R. M., Liao, Y.-S. J., Balazic, E., Cowart, J. R., Arocha, R., Redler, T., Febo, M., et al. (2019) · Acta Physiologica · doi:10.1111/apha.13256 · Cited by 116 · see citing works
Short chain fatty acids in plasma and brain: Quantitative determination by gas chromatography
Bachmann, C., Colombo, J.-P., & Berüter, J. (1979) · Clinica Chimica Acta · doi:10.1016/0009-8981(79)90109-8 · Cited by 115 · see citing works
Anti-Depressant Fluoxetine Reveals its Therapeutic Effect Via Astrocytes
Kinoshita, M., Hirayama, Y., Fujishita, K., Shibata, K., Shinozaki, Y., Shigetomi, E., Takeda, A., Le, H. P. N., Hayashi, H., Hiasa, M., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.05.036 · Cited by 115 · see citing works
Rethinking individuality: the dialectics of the holobiont
Gilbert, S. F., & Tauber, A. I. (2016) · Biology & Philosophy · doi:10.1007/s10539-016-9541-3 · Cited by 99 · see citing works
Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
Jun, M., Xiaolong, Q., Chaojuan, Y., Ruiyuan, P., Shukun, W., Junbing, W., Li, H., Hong, C., Jinbo, C., Rong, W., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.229 · Cited by 95 · see citing works
Valvassori, S. S., Varela, R. B., Arent, C. O., Dal-Pont, G. C., Bobsin, T. S., Budni, J., Réus, G. Z., & Quevedo, J. (2014) · Current Neurovascular Research · doi:10.2174/1567202611666140829162158 · Cited by 86 · see citing works
Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors
Boué‐Grabot, É., & Pankratov, Y. (2017) · Neural Plasticity · doi:10.1155/2017/9454275 · Cited by 86 · see citing works
Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells.
Dedkova, E. N., Sigova, A. A., & Зинченко, В. П. (2000) · PubMed · Cited by 84 · see citing works
Wang, C., Zheng, D., Weng, F., Jin, Y., & He, L. (2021) · Psychopharmacology · doi:10.1007/s00213-021-06025-0 · Cited by 76 · see citing works
Spichak, S., Donoso, F., Moloney, G. M., Gunnigle, E., Brown, J. R.-M., Codagnone, M. G., Dinan, T. G., & Cryan, J. F. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100318 · Cited by 73 · see citing works
Resende, W. R., Valvassori, S. S., Réus, G. Z., Varela, R. B., Arent, C. O., Ribeiro, K. F., Bavaresco, D. V., Andersen, M. L., Zugno, A. I., & Quevedo, J. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32836546fc · Cited by 65 · see citing works
Dehghani, F., Abdollahi, S., Shidfar, F., Clark, C. C. T., & Soltani, S. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2022.2110664 · Cited by 65 · see citing works
Garcez, M., Tan, V., Heng, B., & Guillemin, G. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920978404 · Cited by 58 · see citing works
Rothhammer, V., Kenison, J. E., Li, Z., Tjon, E. C., Takenaka, M. C., Chao, C., de Lima, K. A., Borucki, D. M., Kaye, J., & Quintana, F. J. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000946 · Cited by 57 · see citing works
Probiotics Affect One‐Carbon Metabolites and Catecholamines in a Genetic Rat Model of Depression
Tillmann, S., Awwad, H. M., Eskelund, A., Treccani, G., Geisel, J., Wegener, G., & Obeid, R. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201701070 · Cited by 52 · see citing works
Miletta, M. C., Petkovic, V., Eblé, A., Ammann, R. A., Flück, C. E., & Mullis, P.-E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107388 · Cited by 51 · see citing works
Zhu, H., Huang, Q., Xu, H., Niu, L., & Zhou, J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.08.039 · Cited by 50 · see citing works
Ca2+-Dependent and Ca2+-Independent ATP Release in Astrocytes
Xiong, Y., Sun, S., Teng, S., Jin, M., & Zhou, Z. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00224 · Cited by 49 · see citing works
Valvassori, S., Resende, W., Budni, J., Dal-Pont, G., Bavaresco, D., Reus, G., Carvalho, A., Goncalves, C., Furlanetto, C., Streck, E., et al. (2015) · Current Neurovascular Research · doi:10.2174/1567202612666150728121121 · Cited by 48 · see citing works
Erratum: Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
Jun, M., Xiaolong, Q., Chaojuan, Y., Ruiyuan, P., Shukun, W., Junbing, W., Li, H., Hong, C., Jinbo, C., Rong, W., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.254 · Cited by 38 · see citing works
Yang, T., Rodríguez, V., Malphurs, W. L., Schmidt, J. T., Ahmari, N., Sumners, C., Martyniuk, C. J., & Zubcevic, J. A. (2018) · Physiological Reports · doi:10.14814/phy2.13732 · Cited by 37 · see citing works
Impaired ATP Release from Brain Astrocytes May be a Cause of Major Depression
Illés, P., Rubini, P., Yin, H., & Tang, Y. (2020) · Neuroscience Bulletin · doi:10.1007/s12264-020-00494-7 · Cited by 37 · see citing works
Grković, I., Drakulić, D., Martinović, J., & Mitrović, N. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170518151541 · Cited by 36 · see citing works
Anderson, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010587 · Cited by 36 · see citing works
Glial Purinergic Signals and Psychiatric Disorders
Koizumi, S. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.822614 · Cited by 28 · see citing works
Histamine elicits glutamate release from cultured astrocytes
Kárpáti, A., Yoshikawa, T., Nakamura, T., Iida, T., Matsuzawa, T., Kitano, H., Harada, R., & Yanai, K. (2018) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2018.05.002 · Cited by 27 · see citing works
Gintonin stimulates gliotransmitter release in cortical primary astrocytes
Kim, H., Lee, B.-H., Choi, S.-H., Kim, H., Jung, S., Hwang, S., Rhim, H., Kim, H.-C., Cho, I., & Nah, S.-Y. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.07.012 · Cited by 22 · see citing works
Huang, Y., Hung, C., Hsu, P.-C., Lee, P., Tsai, Y., Hsin, Y., Lee, X., Chou, C., Chen, M., Tarng, D., et al. (2022) · Glia · doi:10.1002/glia.24326 · Cited by 15 · see citing works
Amyloid pathology disrupts gliotransmitter release in astrocytes
Pillai, A. G., & Nadkarni, S. (2022) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010334 · Cited by 12 · see citing works
Ohmomo, H., Ehara, A., Yoshida, S., Shutoh, F., Ueda, S., & Hisano, S. (2011) · Neuroscience Research · doi:10.1016/j.neures.2011.05.005 · Cited by 5 · see citing works
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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 · see citing works
- Authors
- Karbownik, M. S., Sokołowska, P., & Kowalczyk, E.
- Affiliations
- Medical University of Lodz (PL)
- Corresponding author
- Karbownik, Michał Seweryn
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-04-01
- Volume
- 24
- Issue
- 7
- Pages
- 6617
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10095279
- OpenAlex
- W4362589214
- Cited by
- 6
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Center of Poland (2021/05/X/NZ3/00557, 503/5-108-03/503-51-001-19-00)
- Medical University of Lodz (2021/05/X/NZ3/00557, 503/5-108-03/503-51-001-19-00)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota metabolites, butyrate, indole-3-propionic acid, astrocytes, gliotransmitters, ATP release, glutamate release, calcium mobilization, gut-brain axis, antidepressants
- MeSH terms
- Gastrointestinal Microbiome, Adenosine Triphosphate, Astrocytes, Humans, Propionates, Glutamic Acid
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