Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain
Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain
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DOI：
10.1016/j.bbi.2019.04.006
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发表时间：
2020-03-01
影响因子：
15.1
通讯作者：
Maione, Sabatino
中科院分区：
文献类型：
--
作者：
Guida, Francesca;Boccella, Serena;Maione, Sabatino
最近的证据表明，肠道微生物区系是大脑和行为的调节器，尽管肠道细菌是否在慢性疼痛中发挥作用仍有待确定。内源性大麻素系统与肠道和中枢神经系统(CNS)水平的炎症和慢性疼痛处理有关。在本研究中，我们使用小鼠低维生素D饮食摄入量，并评估了肠道微生物区系、疼痛处理和内源性大麻素系统信号的可能变化。维生素D缺乏导致微生物多样性降低，其特征是微生物数量增加，蠕形杆菌和类杆菌减少。同时，维生素D缺乏的小鼠表现出与脊髓水平的神经元超兴奋性和内源性大麻系统成员(内源性介质及其受体)变化相关的触觉异常。在十二指肠和结肠中也观察到内源性大麻素水平的变化。值得注意的是，与赋形剂治疗的小鼠相比，抗炎性大麻酰胺的同系物棕榈酰乙醇胺抑制了缺乏维生素D的小鼠的疼痛行为和脊髓生化变化，同时增加了Akkermansia、真细菌和肠杆菌的水平。最后，在正常或维生素D缺乏的小鼠中，诱导备用神经损伤并不伴随肠道微生物区系的变化。我们的数据表明，维生素D缺乏和肠道细菌组成的相关变化与伤害性改变之间存在联系，可能是通过涉及内源性大麻素和相关介质信号系统的分子机制。
Recent evidence points to the gut microbiota as a regulator of brain and behavior, although it remains to be determined if gut bacteria play a role in chronic pain. The endocannabinoid system is implicated in inflammation and chronic pain processing at both the gut and central nervous system (CNS) levels. In the present study, we used low Vitamin D dietary intake in mice and evaluated possible changes in gut microbiota, pain processing and endocannabinoid system signaling.Vitamin D deficiency induced a lower microbial diversity characterized by an increase in Firmicutes and a decrease in Verrucomicrobia and Bacteroidetes. Concurrently, vitamin D deficient mice showed tactile allodynia associated with neuronal hyperexcitability and alterations of endocannabinoid system members (endogenous mediators and their receptors) at the spinal cord level. Changes in endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were also observed in the duodenum and colon.Remarkably, the anti-inflammatory anandamide congener, palmitoylethanolamide, counteracted both the pain behaviour and spinal biochemical changes in vitamin D deficient mice, whilst increasing the levels of Akkermansia, Eubacterium and Enterobacteriaceae, as compared with vehicle-treated mice. Finally, induction of spared nerve injury in normal or vitamin D deficient mice was not accompanied by changes in gut microbiota composition.Our data suggest the existence of a link between Vitamin D deficiency - with related changes in gut bacterial composition - and altered nociception, possibly via molecular mechanisms involving the endocannabinoid and related mediator signaling systems.