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- Title
GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine.
- Authors
Pokusaeva, K.; Johnson, C.; Luk, B.; Uribe, G.; Fu, Y.; Oezguen, N.; Matsunami, R. K.; Lugo, M.; Major, A.; Mori‐Akiyama, Y.; Hollister, E. B.; Dann, S. M.; Shi, X. Z.; Engler, D. A.; Savidge, T.; Versalovic, J.
- 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. dentium ATCC 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.
- Subjects
GABA; BIFIDOBACTERIUM; HUMAN microbiota; NEUROTRANSMITTERS; ABDOMINAL pain
- Publication
Neurogastroenterology & Motility, 2017, Vol 29, Issue 1, pn/a
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/nmo.12904