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

GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine.

Author information

1
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
2
Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
3
Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA.
4
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
5
Proteomics Programmatic Core Laboratory, Houston Methodist Hospital Research Institute, Houston, TX, USA.

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.

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

PMID:
27458085
PMCID:
PMC5195897
DOI:
10.1111/nmo.12904
[Indexed for MEDLINE]
Free PMC Article

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