1398-P: Lactobacillus rhamnosus Attenuates Depressive-Like Behavior in High-Fat Diet Fed Mice and Regulates Tyrosine Hydroxylase

Abstract

Prevalence of depression is higher in diabetic patients compared to healthy humans due to a shared pathogenesis including insulin resistance and inflammation. These factors are also linked to intestinal dysbiosis. Interestingly, preventive intake of probiotic lactobacilli has been shown to improve dysbiosis along with mood and metabolism. Yet, a potential therapeutic role and underlying mechanism of Lactobacillus rhamnosus GG (LGG, ATCC 53103) to improve emotional behavior in diet-induced obesity is unknown. Male C57BL/6N mice were fed a low-fat diet (LFD, 10% kcal from fat) or high-fat diet (HFD, 45% kcal from fat) for 6 weeks and followed by daily oral gavage of vehicle or 1x108 CFU of LGG. Dark-Light Box Test was used to evaluate anxiety, Mousetail Suspension Test (MST) and Splash Test were used to assess depressive-like behavior and motivation for self-care. Cecal microbiome composition was analyzed using 16S rRNA Sequencing. Plasma and CSF were collected for metabolomic analysis, and gene expression was analyzed using qPCR. We observed that 12 weeks of HFD feeding increased anxiety and depressive-like behavior. Strikingly, LGG decreased specifically depressive-like behavior in the MST which was confirmed by the Splash Test. Metagenomics analysis revealed that HFD but not LGG alters cecal microbiome composition, indicating a transient effect. Moreover, HFD feeding significantly altered plasma lipid metabolism whereas LGG decreased branched chain amino acids which associated with improved emotional behavior. In dopaminergic brain regions, LGG restored the HFD-induced decrease of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, while not altering enzymes responsible for dopamine degradation. Our data indicate that LGG attenuates specifically depressive-like behavior in HFD-fed mice with a molecular signature of restored dopamine synthesis. Disclosure M.Schell: Other Relationship; Novozymes A/S, Denmark. K.Wardelmann: None. R.Hauffe: None. M.Rath: None. S.Chopra: None. A.Kleinridders: Other Relationship; Novozymes. Funding German Ministry of Education and Research (BMBF) and the State of Brandenburg (DZD grant 82DZD00302 and BMBF grant 031B0569) .