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Brain Behav Immun. 2019 Apr 3. pii: S0889-1591(18)31247-9. doi: 10.1016/j.bbi.2019.04.006. [Epub ahead of print]

Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain.

Author information

1
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: franc.guida@gmail.com.
2
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
3
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
4
Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy; Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy.
5
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy; Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Quèbec Heart and Lung Institute and Institute for Nutrition and Functional Foods, Université Laval, 2325 Rue de l'Université, Québec, QC G1V 0A6, Canada. Electronic address: vdimarzo@icb.cnr.it.
6
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: sabatino.maione@unicampania.it.

Abstract

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.

KEYWORDS:

Endocannabinoids; Gut microbiota; Pain; Vitamin D deficiency

PMID:
30953765
DOI:
10.1016/j.bbi.2019.04.006
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