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

32 Citations (Scopus)

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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Bifidobacterium
gamma-Aminobutyric Acid
Intestines
Abdominal Pain
Hypersensitivity
Pain Perception
Neurotransmitter Agents
Oral Administration
Visceral Pain
Aminobutyrates
Bacteria
Afferent Neurons
Decarboxylation
Brain
Insurance Benefits
Sensory Receptor Cells
Analgesics
Glutamic Acid
Delivery of Health Care
Pain

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., ... 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

GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. / 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, Sara; Shi, Xuan-Zheng; Engler, D. A.; Savidge, T.; Versalovic, J.

In: Neurogastroenterology and Motility, Vol. 29, No. 1, e12904, 01.01.2017.

Research output: Contribution to journalArticle

Pokusaeva, K, Johnson, C, Luk, B, Uribe, G, Fu, Y, Oezguen, N, Matsunami, RK, Lugo, M, Major, A, Mori-Akiyama, Y, Hollister, EB, Dann-Grice, S, Shi, X-Z, Engler, DA, Savidge, T & Versalovic, J 2017, 'GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine', Neurogastroenterology and Motility, vol. 29, no. 1, e12904. https://doi.org/10.1111/nmo.12904
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, Sara ; Shi, Xuan-Zheng ; Engler, D. A. ; Savidge, T. ; Versalovic, J. / GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. In: Neurogastroenterology and Motility. 2017 ; Vol. 29, No. 1.
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AU - Johnson, C.

AU - Luk, B.

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AU - Oezguen, N.

AU - Matsunami, R. K.

AU - Lugo, M.

AU - Major, A.

AU - Mori-Akiyama, Y.

AU - Hollister, E. B.

AU - Dann-Grice, Sara

AU - Shi, Xuan-Zheng

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AU - Savidge, T.

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AB - 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.

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