Cerebral low-molecular metabolites influenced by intestinal microbiota: a pilot study
Open accessAbstract
Recent studies suggest that intestinal microbiota influences gut-brain communication. In this study, we aimed to clarify the influence of intestinal microbiota on cerebral metabolism. We analyzed the cerebral metabolome of germ-free (GF) mice and Ex-GF mice, which were inoculated with suspension of feces obtained from specific pathogen-free mice, using capillary electrophoresis with time-of-flight mass spectrometry (CE-TOFMS). CE-TOFMS identified 196 metabolites from the cerebral metabolome in both GF and Ex-GF mice. The concentrations of 38 metabolites differed significantly (p < 0.05) between GF and Ex-GF mice. Approximately 10 of these metabolites are known to be involved in brain function, whilst the functions of the remainder are unclear. Furthermore, we observed a novel association between cerebral glycolytic metabolism and intestinal microbiota. Our work shows that cerebral metabolites are influenced by normal intestinal microbiota through the microbiota-gut-brain axis, and indicates that normal intestinal microbiota closely connected with brain health and disease, development, attenuation, learning, memory, and behavior.
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Several metabolomic studies show alterations in the dopamine and serotonin systems in germ-free animals.
“Several metabolomic studies show alterations in the dopamine and serotonin systems (124, 189, 350, 378–380).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [380]
These changes include increased hippocampal dopamine D1 receptor mRNA levels, decreased dopamine D1 receptor in the striatum and nucleus accumbens, increased serotonin in the blood and hippocampus, and decreased serotonin receptor expression.
“These changes include increased hippocampal dopamine D1 receptor mRNA levels and decreased dopamine D1 receptor in the striatum and nucleus accumbens, as well as increased serotonin in the blood and hippocampus, with decreased serotonin receptor expression, respectively.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [380]
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Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · see citing works
Host-Bacterial Mutualism in the Human Intestine
Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1104816 · Cited by 5,277 · see citing works
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · see citing works
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228 · see citing works
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735 · see citing works
Self-citationNeufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01620.x · Cited by 1,392 · see citing works
Principles and clinical implications of the brain-gut-enteric microbiota axis
Rhee, S. H., Pothoulakis, C., & Mayer, E. A. (2009) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.35 · Cited by 1,342 · cited 4× · see citing works
“The results of these studies suggest that intestinal microbiota have a great impact on gut-brain communication, which led to the coining of the term “microbiota-gut-brain axis” (MGB axis) (Rhee et al., 2009; Cryan and Dinan, 2012).”
InfluentialTyrosine hydroxylase and regulation of dopamine synthesis
Daubner, S. C., Le, T., & Wang, S. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.12.017 · Cited by 1,092 · see citing works
Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies
Simmons, M. L., Frondoza, C. G., & Coyle, J. T. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90101-s · Cited by 631 · see citing works
Branched-Chain Amino Acids and Brain Function
Fernstrom, J. D. (2005) · The Journal of Nutrition · doi:10.1093/jn/135.6.1539s · Cited by 514 · see citing works
Jéquier, E., Lovenberg, W. M., & Sjoerdsma, A. (1967) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)14792-5 · Cited by 425 · see citing works
Impact of intestinal microbiota on intestinal luminal metabolome
Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Kurihara, S., Sawaki, E., Koga, Y., & Benno, Y. (2012) · Scientific Reports · doi:10.1038/srep00233 · Cited by 334 · see citing works
Self-citationMetabolome analysis by capillary electrophoresis–mass spectrometry
Monton, M. R. N., & Soga, T. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2007.02.065 · Cited by 319 · see citing works
Matsumoto, M., Kurihara, S., Kibe, R., Ashida, H., & Benno, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023652 · Cited by 290 · cited 2× · see citing works
“Recently, the relationship between intestinal microbiota and systemic phenomena beyond the intestinal environment, such as obesity (Turnbaugh et al., 2006) and lifespan (Matsumoto et al., 2011), have been reported.”
Self-citationDietary sialic acid supplementation improves learning and memory in piglets
Wang, B., Yu, B., Karim, M., Hu, H., Sun, Y. W., McGreevy, P. D., Petocz, P., Held, S. D. E., & Brand-Miller, J. C. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.2.561 · Cited by 288 · see citing works
Blood-Brain Barrier Carrier-Mediated Transport and Brain Metabolism of Amino Acids
Pardridge, W. M. (1998) · Neurochemical Research · doi:10.1023/a:1022482604276 · Cited by 281 · see citing works
Tyrosine Hydroxylase and Parkinson’s Disease
Haavik, J., & Toska, K. (1998) · Molecular Neurobiology · doi:10.1007/bf02741387 · Cited by 263 · see citing works
Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia
Ooga, T., Sato, H., Nagashima, A., Sasaki, K., Tomita, M., Soga, T., & Ohashi, Y. (2011) · Molecular BioSystems · doi:10.1039/c0mb00141d · Cited by 215 · see citing works
Self-citationFeedback interactions in the control of citric acid cycle activity in rat heart mitochondria
LaNoue, K. F., Bryla, J., & Williamson, J. R. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45660-3 · Cited by 181 · see citing works
Jenkins, B. G., Klivènyi, P., Küstermann, E., Andreassen, O. A., Ferrante, R. J., Rosen, B. R., & Beal, M. F. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0742108.x · Cited by 170 · see citing works
Yang, J. H., Wada, A., Yoshida, K., Miyoshi, Y., Sayano, T., Esaki, K., Kinoshita, M. O., Tomonaga, S., Azuma, N., Watanabe, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.187443 · Cited by 147 · see citing works
Cámara, R. J. A., Ziegler, R., Begré, S., Schoepfer, A. M., & von Känel, R. (2009) · Digestion · doi:10.1159/000226087 · Cited by 106 · see citing works
Rapid metabolic evolution in human prefrontal cortex
Fu, X., Giavalisco, P., Liu, X., Catchpole, G., Fu, N., Ning, Z., Guo, S., Zheng, Y., Somel, M., Pääbo, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019164108 · Cited by 99 · see citing works
Normal gut microbiota modulates brain development and behavior
Neu, J. (2012) · Yearbook of Neonatal and Perinatal Medicine · doi:10.1016/j.ynpm.2011.10.003 · Cited by 89 · see citing works
Sugiura, Y., Taguchi, R., & Setou, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017952 · Cited by 77 · see citing works
Carlson, S. E., & House, S. G. (1986) · Journal of Nutrition · doi:10.1093/jn/116.5.881 · Cited by 66 · see citing works
Electrophoretic study of pipecolic acid, a biogenic imino acid, in the mammalian brain
Kasé, Y., Takahama, K., Hashimoto, T., et al. (1980) · Brain Research · doi:10.1016/0006-8993(80)90199-7 · Cited by 44 · see citing works
Pipecolic acid induces apoptosis in neuronal cells
Matsumoto, S., Yamamoto, S., Sai, K., et al. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02869-5 · Cited by 30 · see citing works
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Neurotransmitter modulation by the gut microbiota
Strandwitz, P. (2018) · Brain Research · doi:10.1016/j.brainres.2018.03.015 · Cited by 1,527 · see citing works
Stress & the gut-brain axis: Regulation by the microbiome
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2017.03.001 · Cited by 1,150 · see citing works
Collective unconscious: How gut microbes shape human behavior
Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.021 · Cited by 571 · see citing works
The maternal microbiome modulates fetal neurodevelopment in mice
Vuong, H. E., Pronovost, G. N., Williams, D. W., Coley, E. J. L., Siegler, E. L., Qiu, A., Kazantsev, M., Wilson, C. J., Rendon, T., & Hsiao, E. Y. (2020) · Nature · doi:10.1038/s41586-020-2745-3 · Cited by 564 · see citing works
Microbiota-gut-brain axis: Modulator of host metabolism and appetite
van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Nutrition · doi:10.3945/jn.116.240481 · Cited by 461 · see citing works
Gut microbiota and the neuroendocrine system
Farzi, A., Fröhlich, E. E., & Holzer, P. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0600-5 · Cited by 478 · see citing works
Gut Bacteria and Neurotransmitters
Dicks, L. M. T. (2022) · Microorganisms · doi:10.3390/microorganisms10091838 · Cited by 482 · see citing works
Microbiota-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 · see citing works
Neuropeptides and the Microbiota-Gut-Brain Axis
Holzer, P., & Farzi, A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_9 · Cited by 451 · see citing works
The microbiome: stress, health and disease
Moloney, R. D., Desbonnet, L., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Mammalian Genome · doi:10.1007/s00335-013-9488-5 · Cited by 430 · see citing works
Signalling 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 · see citing works
Gut 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 · see citing works
Alzheimer’s disease and gut microbiota
Hu, X., Wang, T., & Jin, F. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-5083-9 · Cited by 371 · see citing works
The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective
Cussotto, S., Sandhu, K. V., Dinan, T. G., & Cryan, J. F. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.04.002 · Cited by 326 · see citing works
“gut microbiota is able to modulate the central levels of catecholamines (Matsumoto et al., 2013).”
BackgroundGut microbiota role in irritable bowel syndrome: New therapeutic strategies
Distrutti, E., Monaldi, L., Ricci, P., & Fiorucci, S. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i7.2219 · Cited by 320 · see citing works
Modulation of Gut Microbiota–Brain Axis by Probiotics, Prebiotics, and Diet
Liu, X., Cao, S., & Zhang, X. (2015) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5b02404 · Cited by 304 · see citing works
Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases
Spielman, L. J., Gibson, D. L., & Klegeris, A. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.08.005 · Cited by 266 · see citing works
The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder
Li, Q., & Zhou, J.-M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.03.013 · Cited by 253 · see citing works
Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication
El Aidy, S., Dinan, T. G., & Cryan, J. F. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.03.002 · Cited by 215 · see citing works
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
Microbiota-gut-brain axis and cognitive function
Gareau, M. G. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_16 · Cited by 189 · see citing works
Goyal, M. S., Venkatesh, S., Milbrandt, J., Gordon, J. I., & Raichle, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511465112 · Cited by 141 · see citing works
The role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
Gao, K., Pi, Y., Mu, C., Peng, Y., Huang, Z., & Zhu, W. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14333 · Cited by 119 · see citing works
Matsumoto, M., Ooga, T., Kibe, R., Aiba, Y., Koga, Y., & Benno, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169207 · Cited by 80 · see citing works
Self-citationGonzalez-Riano, C., Saiz, J., Barbas, C., Bergareche, A., Huerta, J. M., Ardanaz, E., Konjevod, M., Mondragon, E., Erro, M. E., Chirlaque, M. D., et al. (2021) · npj Parkinson's Disease · doi:10.1038/s41531-021-00216-4 · Cited by 49 · see citing works
Zhang, X., Wang, H., Kilpatrick, L. A., Dong, T. S., Gee, G. C., Labus, J. S., Osadchiy, V., Beltran-Sanchez, H., Wang, M. C., Vaughan, A., et al. (2023) · Nature Mental Health · doi:10.1038/s44220-023-00134-9 · Cited by 20 · see citing works
- Authors
- Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Sawaki, E., Koga, Y., & Benno, Y.
- Affiliations
- RIKEN (JP)
- Human Metabolome Technologies, Inc. (Japan) (JP)
- Tokai University (JP)
- Corresponding author
- Matsumoto, Mitsuharu
- Venue
- Frontiers in Systems Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 9-9
- ISSN
- 1662-5137 (ISSN-L)
- PMC
- PMC3632785
- OpenAlex
- W2140366570
- Cited by
- 227
- References
- 28
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 10 · 2023: 20 · 2022: 26 · 2021: 32 · 2020: 25 · 2019: 14 · 2018: 22 · 2017: 17 · 2016: 19 · 2015: 10 · 2014: 9 · 2013: 2
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Systems Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Bio-oriented Technology Research Advancement Institution
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, microbiota-gut-brain axis, low molecular weight metabolites, germ-free mice, fecal microbiota transplantation, brain health, brain function
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