A Probiotic Mixture Induces Anxiolytic- and Antidepressive-Like Effects in Fischer and Maternally Deprived Long Evans Rats

Valérie Daugé; Catherine Philippe; Mahendra Mariadassou; Olivier Rué; Jean-Charles Martin; Marie-Noelle Rossignol; Nathalie Dourmap; Ljubica Svilar; Franck Tourniaire; Magali Monnoye; Deborah Jardet; Marie Bangratz; Sophie Holowacz; Sylvie Rabot; Laurent Naudon

doi:10.3389/fnbeh.2020.581296

A Probiotic Mixture Induces Anxiolytic- and Antidepressive-Like Effects in Fischer and Maternally Deprived Long Evans Rats

Front Behav Neurosci. 2020 Nov 12:14:581296. doi: 10.3389/fnbeh.2020.581296. eCollection 2020.

Authors

Affiliations

¹ Université Paris-Saclay, INRAE, AgroParisTech, CNRS, Micalis Institute, Jouy-en-Josas, France.
² Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.
³ Université Paris-Saclay, INRAE, BioinfOmics, MIGALE Bioinformatics Facility, Jouy-en-Josas, France.
⁴ Université Aix Marseille, C2VN, CRIBIOM, Marseille, France.
⁵ Université Paris-Saclay, INRAE, MaIAGE, Jouy-en-Josas, France.
⁶ UNIROUEN, UFR Médecine-Pharmacie, Inserm U 1245 Team 4, Rouen, France.
⁷ Université Aix Marseille, C2VN, Marseille, France.
⁸ PiLeJe Laboratoire, Paris, France.

Abstract

A role of the gut microbiota in psychiatric disorders is supported by a growing body of literature. The effects of a probiotic mixture of four bacterial strains were studied in two models of anxiety and depression, naturally stress-sensitive Fischer rats and Long Evans rats subjected to maternal deprivation. Rats chronically received either the probiotic mixture (1.10⁹ CFU/day) or the vehicle. Anxiety- and depressive-like behaviors were evaluated in several tests. Brain monoamine levels and gut RNA expression of tight junction proteins (Tjp) and inflammatory markers were quantified. The gut microbiota was analyzed in feces by 16S rRNA gene sequencing. Untargeted metabolite analysis reflecting primary metabolism was performed in the cecal content and in serum. Fischer rats treated with the probiotic mixture manifested a decrease in anxiety-like behaviors, in the immobility time in the forced swimming test, as well as in levels of dopamine and its major metabolites, and those of serotonin metabolites in the hippocampus and striatum. In maternally deprived Long Evans rats treated with the probiotic mixture, the number of entries into the central area in the open-field test was increased, reflecting an anxiolytic effect. The probiotic mixture increased Tjp1 and decreased Ifnγ mRNA levels in the ileum of maternally deprived rats. In both models, probiotic supplementation changed the proportions of several Operational Taxonomic Units (OTU) in the gut microbiota, and the levels of certain cecal and serum metabolites were correlated with behavioral changes. Chronic administration of the tested probiotic mixture can therefore beneficially affect anxiety- and depressive-like behaviors in rats, possibly owing to changes in the levels of certain metabolites, such as 21-deoxycortisol, and changes in brain monoamines.

Keywords: anxiety-like behavior; brain; depressive-like behavior; gut junction protein RNAs; maternal deprivation; metabolites; monoamines; probiotic.