title: GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine.
abstract: BACKGROUND
  Recurrent abdominal pain is a common and costly health-care problem attributed, in part, to visceral hypersensitivity. Increasing evidence suggests that gut bacteria contribute to abdominal pain perception by modulating the microbiome-gut-brain axis. However, specific microbial signals remain poorly defined. γ-aminobutyric acid (GABA) is a principal inhibitory neurotransmitter and a key regulator of abdominal and central pain perception from peripheral afferent neurons. Although gut bacteria are reported to produce GABA, it is not known whether the microbial-derived neurotransmitter modulates abdominal pain.
  
  
  METHODS
  To investigate the potential analgesic effects of microbial GABA, we performed daily oral administration of a specific Bifidobacterium strain (B. dentiumATCC 27678) in a rat fecal retention model of visceral hypersensitivity, and subsequently evaluated pain responses.
  
  
  RESULTS
  We demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.
  
  
  CONCLUSIONS
  The functional significance of microbial-derived GABA was demonstrated by gadB-dependent desensitization of colonic afferents in a murine model of visceral hypersensitivity. Visceral pain modulation represents another potential health benefit attributed to bifidobacteria and other GABA-producing species of the intestinal microbiome. Targeting GABAergic signals along this microbiome-gut-brain axis represents a new approach for the treatment of abdominal pain.
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: K
authors.initials: K
authors.lastname: Pokusaeva
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Luk
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Uribe
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Oezguen
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Matsunami
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lugo
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Major
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori-Akiyama
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Hollister
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Dann
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Shi
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Engler
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Savidge
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.|Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001483:Base Sequence; D001644:Bifidobacterium / Q000235:genetics; D002460:Cell Line; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D059265:Visceral Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000096:biosynthesis*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: 
  Bifidobacterium
  ; 
  GABA
  ; brain gut axis; microbiome; neuromodulation