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Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate
Abstract
The gut microbiome has been shown to regulate the development and functions of the enteric and central nervous systems. Its involvement in the regulation of behavior has attracted particular attention because of its potential translational importance in clinical disorders, however little is known about the pathways involved. We previously have demonstrated that administration of Lactobacillus rhamnosus (JB-1) to healthy male BALB/c mice, promotes consistent changes in GABA-A and -B receptor sub-types in specific brain regions, accompanied by reductions in anxiety and depression-related behaviors. In the present study, using magnetic resonance spectroscopy (MRS), we quantitatively assessed two clinically validated biomarkers of brain activity and function, glutamate+glutamine (Glx) and total N-acetyl aspartate+N-acetyl aspartyl glutamic acid (tNAA), as well as GABA, the chief brain inhibitory neurotransmitter. Mice received 1×10(9) cfu of JB-1 per day for 4weeks and were subjected to MRS weekly and again 4weeks after cessation of treatment to ascertain temporal changes in these neurometabolites. Baseline concentrations for Glx, tNAA and GABA were equal to 10.4±0.3mM, 8.7±0.1mM, and 1.2±0.1mM, respectively. Delayed increases were first seen for Glx (~10%) and NAA (~37%) at 2weeks which persisted only to the end of treatment. However, Glx was still elevated 4weeks after treatment had ceased. Significantly elevated GABA (~25%) was only seen at 4weeks. These results suggest specif…
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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
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
Self-citationNormal 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
The gut flora as a forgotten organ
O'Hara, A. M., & Shanahan, F. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400731 · Cited by 2,791
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
The gut microbiota influences blood-brain barrier permeability in mice
Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., Korecka, A., Bakocevic, N., Ng, L. G., Kundu, P., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009759 · Cited by 2,530
Gut–brain axis: How the microbiome influences anxiety and depression
Foster, J. A., & McVey Neufeld, K.-A. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.01.005 · Cited by 2,460 · cited 4×
“…to alterations in emotional behavior, and structural and functional aspects of brain activity (Bercik et al., 2011; Bravo et al., 2011; Collins et al., 2012; Cryan and Dinan, 2012; Diaz Heijtz et al., 2011; Dinan et al., 2013; Forsythe and Kunze, 2013; Foster and Neufeld, 2013; Mayer et al., 2014).”
BackgroundInfluentialMicrobiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., & Mithieux, G. (2014) · Cell · doi:10.1016/j.cell.2013.12.016 · Cited by 2,200
Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.052 · Cited by 1,748
Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution
Zilber-Rosenberg, I., & Rosenberg, E. (2008) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2008.00123.x · Cited by 1,739
The interplay between the intestinal microbiota and the brain
Collins, S. M., Surette, M., & Bercik, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2876 · Cited by 1,611 · cited 3×
“…or causal to alterations in emotional behavior, and structural and functional aspects of brain activity (Bercik et al., 2011; Bravo et al., 2011; Collins et al., 2012; Cryan and Dinan, 2012; Diaz Heijtz et al., 2011; Dinan et al., 2013; Forsythe and Kunze, 2013; Foster and Neufeld, 2013; Mayer…”
BackgroundSpatial Localization in NMR Spectroscopy in Vivo
Bottomley, P. A. (1987) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1987.tb32915.x · Cited by 1,382
Psychobiotics: A novel class of psychotropic
Dinan, T. G., Stanton, C., & Cryan, J. F. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.001 · Cited by 1,287
Three‐dimensional magnetization‐prepared rapid gradient‐echo imaging (3D MP RAGE)
Mugler, J. P., & Brookeman, J. R. (1990) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910150117 · Cited by 1,276
Gut microbes and the brain: paradigm shift in neuroscience
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3299-14.2014 · Cited by 1,033
In vivo1H NMR spectroscopy of rat brain at 1 ms echo time
Tk�?, I., uk, Z. S., Choi, I., & Rolf Gruetter, A. (1999) · Magnetic Resonance in Medicine · doi:10.1002/(sici)1522-2594(199904)41:4 · Cited by 1,010
The microbiome-gut-brain axis: from bowel to behavior
Cryan, J. F., & O’Mahony, S. M. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01664.x · Cited by 990
The Earth Microbiome project: successes and aspirations
Gilbert, J. A., Jansson, J. K., & Knight, R. D. (2014) · BMC Biology · doi:10.1186/s12915-014-0069-1 · Cited by 917
Hasler, G., van der Veen, J. W., Tumonis, T., Meyers, N., Shen, J., & Drevets, W. C. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.2.193 · Cited by 846
The human gut microbiome: ecology and recent evolutionary changes
Walter, J., & Ley, R. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102830 · Cited by 720
Computer Simulations in Magnetic Resonance. An Object-Oriented Programming Approach
Smith, S. A., Levante, T. O., Meier, B. H., & Ernst, R. R. (1994) · Journal of Magnetic Resonance Series A · doi:10.1006/jmra.1994.1008 · Cited by 711
Groves, D. A., & Brown, V. J. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.01.004 · Cited by 677
The GABA system in anxiety and depression and its therapeutic potential
Möhler, H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.040 · Cited by 627
Impact of consuming a milk drink containing a probiotic on mood and cognition
Benton, D., Williams, C., & Brown, A. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602546 · Cited by 554
Alander, M., Satokari, R. M., Korpela, R., Saxelin, M., Vilpponen-Salmela, T., Mattila, T., & von Wright, A. (1999) · Applied and Environmental Microbiology · doi:10.1128/aem.65.1.351-354.1999 · Cited by 526
Unconstrained parametrizations for variance-covariance matrices
Pinheiro, J. C., & Bates, D. M. (1996) · Statistics and Computing · doi:10.1007/bf00140873 · Cited by 523
Role of the intestinal microbiome in health and disease: from correlation to causation
de Vos, W. M., & de Vos, E. A. (2012) · Nutrition Reviews · doi:10.1111/j.1753-4887.2012.00505.x · Cited by 440
Forsythe, P., Sudo, N., Dinan, T., Taylor, V. H., & Bienenstock, J. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.05.058 · Cited by 429
Self-citationN-Acetylaspartate in the Vertebrate Brain: Metabolism and Function
Baslow, M. H. (2003) · Neurochemical Research · doi:10.1023/a:1023250721185 · Cited by 393
Voices from within: gut microbes and the CNS
Forsythe, P., & Kunze, W. A. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1028-z · Cited by 336
Self-citationWilson, M., Reynolds, G., Kauppinen, R. A., Arvanitis, T. N., & Peet, A. C. (2010) · Magnetic Resonance in Medicine · doi:10.1002/mrm.22579 · Cited by 327
High magnetic field water and metabolite proton T 1 and T 2 relaxation in rat brain in vivo
de Graaf, R. A., Brown, P. B., McIntyre, S., Nixon, T. W., Behar, K. L., & Rothman, D. L. (2006) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20946 · Cited by 305
Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder
Winsberg, M. E., Sachs, N., Tate, D. L., Elfar Adalsteinsson, A., Spielman, D. M., & Ketter, T. A. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00183-3 · Cited by 294
A comparison of cell and tissue extraction techniques using high‐resolution 1H‐NMR spectroscopy
Belle, J. E. L., Harris, N. G., Williams, S. R., & Bhakoo, K. K. (2002) · NMR in Biomedicine · doi:10.1002/nbm.740 · Cited by 292
CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa
Gerner, R. H., & Hare, T. A. (1981) · American Journal of Psychiatry · doi:10.1176/ajp.138.8.1098 · Cited by 259
Luykx, J. J., Laban, K. G., van den Heuvel, M. P., Boks, M. P. M., Mandl, R. C. W., Kahn, R. S., & Bakker, S. C. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.05.014 · Cited by 235
Perez-Burgos, A., Wang, B., Mao, Y.-K., Mistry, B., Neufeld, K.-A. M., Bienenstock, J., & Kunze, W. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00128.2012 · Cited by 235
Self-citationMicrobiota-stimulated immune mechanisms to maintain gut homeostasis
Chung, H., & Kasper, D. L. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.06.008 · Cited by 216
Li, B. S. Y., Wang, H., & Gonen, O. (2003) · Magnetic Resonance Imaging · doi:10.1016/s0730-725x(03)00181-4 · Cited by 207
Demougeot, C., Garnier, P. E., Mossiat, C. M., Bertrand, N., Giroud, M., Beley, A., & Marie, C. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00285.x · Cited by 194
Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T
Tkáč, I., Henry, P., Andersen, P., Keene, C. D., Low, W. C., & Rolf Gruetter, A. (2004) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20184 · Cited by 192
Quantitative proton MRS predicts outcome after traumatic brain injury
Friedman, S. D., Brooks, W. M., Jung, R. E., Chiulli, S. J., Sloan, J. H., Montoya, B. T., Hart, B. L., & Yeo, R. A. (1999) · Neurology · doi:10.1212/wnl.52.7.1384 · Cited by 181
Gideon, P., Henriksen, O. M., Sperling, B. K., Christiansen, P., Olsen, T. S., Jørgensen, H. S., & Arlien-Søborg, P. (1992) · Stroke · doi:10.1161/01.str.23.11.1566 · Cited by 179
Mao, Y.-K., Kasper, D. L., Wang, B., Forsythe, P., Bienenstock, J., & Kunze, W. A. (2013) · Nature Communications · doi:10.1038/ncomms2478 · Cited by 178
Self-citationLongitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease
Elfar Adalsteinsson, A., Sullivan, E. V., Kleinhans, N. M., Spielman, D. M., & Pfefferbaum, A. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02246-7 · Cited by 174
Blood-brain barrier to H3-γ-aminobutyric acid in normal and amino oxyacetic acid-treated animals
Kuriyama, K., & Sze, P. Y. (1971) · Neuropharmacology · doi:10.1016/0028-3908(71)90013-x · Cited by 169
Delayed pharmacological effects of antidepressants
Frazer, A., & Benmansour, S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001015 · Cited by 160
Analysis of gene–environment interactions in postnatal development of the mammalian intestine
Rakoff-Nahoum, S., Kong, Y., Kleinstein, S. H., Subramanian, S., Ahern, P. P., Gordon, J. I., & Medzhitov, R. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424886112 · Cited by 108
Ahlroos, T., & Tynkkynen, S. (2009) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2008.04018.x · Cited by 107
Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
Öberg, J., Spenger, C., Wang, F., Andersson, A. D. R., Westman, E., Skoglund, P., Sunnemark, D., Norinder, U., Klason, T., Wahlund, L., et al. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.002 · Cited by 106
Wang, B., Mao, Y., Diorio, C. J., Pasyk, M., Wu, R., Bienenstock, J., & Kunze, W. (2010) · The FASEB Journal · doi:10.1096/fj.09-153841 · Cited by 98
Self-citationProton T 2 relaxation time of J ‐coupled cerebral metabolites in rat brain at 9.4 T
Xin, L., Gambarota, G., Mlynárik, V., & Rolf Gruetter, A. (2007) · NMR in Biomedicine · doi:10.1002/nbm.1205 · Cited by 79
A Short‐echo‐time Proton Magnetic Resonance Spectroscopic Imaging Study of Temporal Lobe Epilepsy
Simister, R. J., Woermann, F. G., McLean, M. A., Bartlett, P. A., Barker, G. J., & Duncan, J. S. (2002) · Epilepsia · doi:10.1046/j.1528-1157.2002.50701.x · Cited by 68
Optimizing T1-weighted imaging of cortical myelin content at 3.0T
Bock, N. A., Hashim, E., Janik, R., Konyer, N. B., Weiß, M., Stanisz, G. J., Turner, R., & Geyer, S. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.09.051 · Cited by 67
Self-citationModel Building for Nonlinear Mixed-Effects Models
Pinheiro, J. C., Bates, D. M., & Lindstrom, M. J. (1994) · Cited by 55
Localized proton MRS of cerebral metabolite profiles in different mouse strains
Schwarcz, A., Natt, O., Watanabe, T., Boretius, S., Frahm, J., & Michaelis, T. (2003) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10445 · Cited by 53
A novel method for simultaneous 3D B1 and T1 mapping: the method of slopes (MoS)
Chavez, S., & Stanisz, G. J. (2012) · NMR in Biomedicine · doi:10.1002/nbm.2769 · Cited by 26
Self-citationCovariate Model Building in Nonlinear Mixed Effects Models
Ribbing, J. (2007) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 13
Larson-Meyer (2000) · doi:10.1002/(sici)1099-1492(200002)13:1
Research works printed but not linked: 1
- Scheperjans, 2014, Gut microbiota are associated with Parkinson's disease and clinical phenotype—a case–control study, J. Neurol., 261, S488-S488
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Probiotics and prebiotics in intestinal health and disease: from biology to the clinic
Sanders, M. E., Merenstein, D. J., Reid, G., Gibson, G. R., & Rastall, R. A. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0173-3 · Cited by 2,059
Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284
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
GABA-modulating bacteria of the human gut microbiota
Strandwitz, P., Kim, K. H., Terekhova, D., Liu, J. K., Sharma, A., Levering, J., McDonald, D., Dietrich, D., Ramadhar, T. R., Lekbua, A., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0307-3 · Cited by 1,170
Metadata
- Authors
- Janik, R., Thomason, L. A. M., Stanisz, A. M., Forsythe, P., Bienenstock, J., & Stanisz, G. J.
- Affiliations
- University of Toronto (CA)
- Sunnybrook Research Institute (CA)
- St. Joseph’s Healthcare Hamilton (CA)
- Medical University of Lublin (PL)
- Corresponding author
- Stanisz, Greg J.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 125
- Pages
- 988-995
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2191644128
- Cited by
- 283
- References
- 59
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 40 · 2023: 31 · 2022: 47 · 2021: 35 · 2020: 35 · 2019: 25 · 2018: 12 · 2017: 14 · 2016: 8
- FWCI
- 15.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Giovanni and Concetta Guglietti Family Foundation
- McMaster Brain-Body Institute at St. Joseph's Healthcare Hamilton
- US Office of Naval Research (N000141410787)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gut microbiota, oral probiotics, brain GABA, N-acetylaspartate, glutamate, glutamine, neurometabolites, anxiety, depression, GABAA receptor, GABAB receptors, biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Animals, Aspartic Acid, Brain, Brain Chemistry, Enzyme-Linked Immunosorbent Assay, gamma-Aminobutyric Acid, Magnetic Resonance Imaging, Male, Mice, Inbred BALB C, Magnetic Resonance Spectroscopy, Glutamic Acid, Probiotics, Mice, Lacticaseibacillus rhamnosus
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