Probiotic Lactobacilli Ameliorate Antibiotic-Induced Cognitive and Behavioral Impairments in Mice

Abstract

Increasing evidence suggests that the gut microbiota, through the “microbiota–gut–brain axis”, can regulate anxiety, mood, and cognitive abilities such as memory and learning processes. Consistently with this, treatments altering the gut microbiota, such as antibiotics and probiotics, may influence brain function and impact behavior. The mechanisms that underlie the interplay between the intestinal microbiota and the brain have been intensively studied. We aimed to investigate the effects of two probiotic lactobacilli strains, Lacticaseibacillus rhamnosus 12L and Lactiplantibacillus plantarum 8PA3, on behavioral disorders in mice induced by a two-week parenteral treatment with broad-spectrum antibiotics. On completion of the treatment, the mice were subjected to behavioral tests, including the open field test (OFT), novel object recognition test (ORT), and T-maze test. Antibiotic-treated mice demonstrated anxiety-related behavior, decreased cognition, and retarded exploratory activity that were ameliorated by the administration of probiotics. As was determined by high-performance liquid chromatography (HPLC), both tested strains produced serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as dopamine, which was further metabolized into norepinephrine by L. plantarum 8PA3 and epinephrine by L. rhamnosus 12L. Moreover, these lactobacilli were found to harbor catecholamines and 3,4-dihydroxyphenylacetic acid (DOPAC) in their biomass when grown on MRS broth. Additionally, L. plantarum 8PA3 and L. rhamnosus 12L were able to impact oxidative stress via H2O2 production and antioxidant activity, as determined in this study by the ferrous oxidation–xylenol orange (FOX) assay and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, respectively. The results obtained in this study support the role of probiotics as a promising therapeutic for neurological disorders. However, more investigations are required to confirm the clinical significance of this finding.

Keywords

• antibiotics
• probiotics
• lactobacilli
• mice
• gut dysbiosis
• microbiota