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
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
Neurogastroenterol Motil. 2017 Jan;29(1). doi: 10.1111/nmo.12904. Epub 2016 Jul 25.
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.
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.
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.
反复腹痛是一个常见且耗费医疗资源的问题，部分原因是内脏超敏反应。越来越多的证据表明，肠道细菌通过调节微生物-肠道-脑轴来影响腹痛感知。然而，具体的微生物信号仍不清楚。γ-氨基丁酸（GABA）是一种主要的抑制性神经递质，也是外周传入神经元腹痛和中枢疼痛感知的关键调节因子。虽然有报道称肠道细菌能产生GABA，但尚不清楚微生物衍生的神经递质是否能调节腹痛。
为了研究微生物源性GABA的潜在镇痛作用，我们在内脏超敏反应的大鼠粪便潴留模型中每日口服一种特定的双歧杆菌菌株（龋齿双歧杆菌ATCC 27678），随后评估疼痛反应。
我们证明共生的龋齿双歧杆菌通过GadB将谷氨酸酶促脱羧产生GABA。在大鼠粪便潴留内脏超敏反应模型中，每日口服这种特定的双歧杆菌（而非gadB缺陷型）菌株可调节感觉神经元活性。
在内脏超敏反应小鼠模型中，通过gadB依赖性使结肠传入神经脱敏，证明了微生物源性GABA的功能意义。内脏疼痛调节是双歧杆菌和肠道微生物群中其他产生GABA的物种的另一种潜在健康益处。沿着这条微生物-肠道-脑轴靶向GABA能信号代表了一种治疗腹痛的新方法。
