GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine

Neurogastroenterol Motil. 2017 Jan;29(1):e12904. doi: 10.1111/nmo.12904. Epub 2016 Jul 25.


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.

Key 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 & inferences: 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.

Keywords: Bifidobacterium; GABA; brain gut axis; microbiome; neuromodulation.

MeSH terms

  • Abdominal Pain / drug therapy
  • Abdominal Pain / metabolism
  • Abdominal Pain / physiopathology
  • Animals
  • Base Sequence
  • Bifidobacterium* / genetics
  • Cell Line
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Male
  • Mice
  • Protein Structure, Secondary
  • Rats
  • Rats, Sprague-Dawley
  • Visceral Pain / drug therapy
  • Visceral Pain / metabolism*
  • Visceral Pain / physiopathology
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / biosynthesis*


  • gamma-Aminobutyric Acid

Associated data

  • GENBANK/ABIX02000002.1