GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine

K. Pokusaeva, C. Johnson, B. Luk, G. Uribe, Y. Fu, N. Oezguen, R. K. Matsunami, M. Lugo, A. Major, Y. Mori-Akiyama, E. B. Hollister, Sara Dann-Grice, Xuan-Zheng Shi, D. A. Engler, T. Savidge, J. Versalovic

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Article numbere12904
JournalNeurogastroenterology and Motility
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Bifidobacterium
  • brain gut axis
  • GABA
  • microbiome
  • neuromodulation

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

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-Grice, S., Shi, X-Z., Engler, D. A., Savidge, T., & Versalovic, J. (2017). GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterology and Motility, 29(1), [e12904]. https://doi.org/10.1111/nmo.12904