Multistrain probiotic rescinds quinpirole-induced obsessive-compulsive disorder phenotypes by reshaping of microbiota gut-brain axis in rats

Abstract

Obsessive-compulsive disorder (OCD) is a disabling mental condition that poses recurring bothersome intrusive thoughts, obsessions, and compulsions. Considering the positive impact of probiotics on neuropsychiatric disorders, herein, we investigated the effect of multistrain probiotic (Bifidobacterium lactis UBBLa-70, Bacillus coagulans Unique IS-2, Lactobacillus rhamnosus UBLR-58, Lactobacillus plantarum UBLP-40, Bifidobacterium infantis UBBI-01, Bifidobacterium breve UBBr-01, and glutamine) in the management of OCD-like phenotype in rats. Rats injected with quinpirole for 5 weeks showed an increased number of marble burying and self-grooming episodes. Quinpirole-injected animals also did less head dipping in the hole board test and avoided exploration of open spaces in the elevated-plus maze. These repetitive, compulsive, self-directed, and anxiety-like phenotypes were abolished after 8-week of multistrain probiotic treatment. The probiotic formulation also prevented the elevated mRNA expression of interleukin-6, tumor-necrosis factor-α, and C-reactive protein in the amygdala and dysregulated levels of 5-hydroxytryptamine, dopamine, and noradrenaline in the frontal cortex of quinpirole-injected rats. The level of brain-derived neurotrophic factor in the frontal cortex remained unaffected across the groups. The altered levels of goblet cells and crypt-to-villi ratio in quinpirole rats were prevented by multistrain probiotic treatment. The results of 16S-rRNA gene-sequencing of gut microbiota from feces contents revealed an elevation in the abundance of Allobaculum and Bifidobacterium species (specifically Bifidobacterium animalis), while the presence of Lactobacillus species (including Lactobacillus reuteri and Lactobacillus vaginalis) exhibited a decline in quinpirole-induced rats. These results imply that modifying the gut-brain axis may be a possible mechanism by which selective multistrain probiotic therapy prevents OCD-like behaviors.

Keywords: Cytokines; Gut-brain axis; Obsessive-compulsive disorder; Probiotic; SCFAs.