title: 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 specific metabolic pathways in our pursuit of mechanisms of action of psychoactive bacteria. They also offer through application of standard clinical neurodiagnostic techniques, translational opportunities to assess biomarkers accompanying behavioral changes induced by alterations in the gut microbiome.
authors.affiliation: Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
authors.forename: Rafal
authors.initials: R
authors.lastname: Janik
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
authors.forename: Lynsie A M
authors.initials: LAM
authors.lastname: Thomason
authors.affiliation: McMaster Brain-Body Institute at St. Joseph's Healthcare Hamilton, T3304, Juravinski Tower, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Stanisz
authors.affiliation: Department of Medicine, McMaster University, St. Joseph's Healthcare Hamilton, T3302, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada; McMaster Brain-Body Institute at St. Joseph's Healthcare Hamilton, T3304, Juravinski Tower, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
authors.affiliation: Department of Pathology, McMaster University, St. Joseph's Healthcare Hamilton,, Juravinski Tower, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada; McMaster Brain-Body Institute at St. Joseph's Healthcare Hamilton, T3304, Juravinski Tower, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Bienenstock
authors.affiliation: Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Neurosurgery and Pediatrics Neurosurgery, Medical University of Lublin, Aleje Raclawickie 1, 20-059 Lublin, Poland. Electronic address: stanisz@sri.utoronto.ca.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stanisz
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D018698:Glutamic Acid / Q000032:analysis / Q000096:biosynthesis*; D052201:Lacticaseibacillus rhamnosus; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019936:Probiotics / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate
keywords: GABA; Glutamate; Magnetic resonance spectroscopy; Microbiome; NAA; Neurotransmitters