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Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice.
Brain Behav Immun 2018, 67:230-245.

Abstract
The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioral, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage. Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioral changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signaling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behavior were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioral, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioral changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations. 

Authors
Guida F, Turco F, Iannotta M, De Gregorio D, Palumbo I, Sarnelli G, Furiano A, Napolitano F, Boccella S, Luongo L, Mazzitelli M, Usiello A, De Filippis F, Iannotti FA, Piscitelli F, Ercolini D, de Novellis V, Di Marzo V, Cuomo R, Maione S

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