Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome

Abstract

Metabolic and neuroactive metabolite production represents one of the mechanisms through which the gut microbiota can impact health. One such metabolite, gamma-aminobutyric acid (GABA), can modulate glucose homeostasis and alter behavioural patterns in the host. We previously demonstrated that oral administration of GABA-producing Lactobacillus brevis DPC6108 has the potential to increase levels of circulating insulin in healthy rats. Therefore, the objective of this study was to assess the efficacy of endogenous microbial GABA production in improving metabolic and behavioural outcomes in a mouse model of metabolic dysfunction. Diet-induced obese and metabolically dysfunctional mice received one of two GABA-producing strains, L. brevis DPC6108 or L. brevis DSM32386, daily for 12 weeks. After 8 and 10 weeks of intervention, the behavioural and metabolic profiles of the mice were respectively assessed. Intervention with both L. brevis strains attenuated several abnormalities associated with metabolic dysfunction, causing a reduction in the accumulation of mesenteric adipose tissue, increased insulin secretion following glucose challenge, improved plasma cholesterol clearance and reduced despair-like behaviour and basal corticosterone production during the forced swim test. Taken together, this exploratory dataset indicates that intervention with GABA-producing lactobacilli has the potential to improve metabolic and depressive- like behavioural abnormalities associated with metabolic syndrome in mice.

Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders

“…These findings suggest that fecal GABA level in the patients with MDD may be modulated by a panel of gut microbes, which may be implicated in the development of MDD. In line with our assumption, a previous study has shown that microbial-derived GABA may influence the host through the gut-brain axis (29), and GABA-producing microbes can improve depression-like behavior (30). Thus, we boldly speculate that the decrease in gut GABA level may be correlated with the dysregulation of GABAergic function in the brain (31).…”

Differences in the Concentration of the Fecal Neurotransmitters GABA and Glutamate Are Associated with Microbial Composition among Healthy Human Subjects

“…It has been reported that mental disorders, such as depression, are negatively correlated with the abundance of GABA-producing Bacteroides [ 14 ]. Further, accumulating evidence from animal trials suggests that the ingestion of GABA-producing bacteria supports relief from psychiatric illnesses, such as depression, and physical ailments, such as diabetes [ 15 , 16 , 17 ]. As the majority of available evidence for GABA’s relation to microbial composition has been performed in animals, there is a need for more evidence from human cohorts to encourage the application of these microbes as probiotic agents.…”

The Decoration of ZnO Nanoparticles by Gamma Aminobutyric Acid, Curcumin Derivative and Silver Nanoparticles: Synthesis, Characterization and Antibacterial Evaluation

“…Gamma-amino butyric acid (GABA), is a small organic molecule composed of amino and carboxylic functional groups. It is a non-protein amino acid that is distributed broadly in biological systems [ 26 ] and a major inhibitory neurotransmitter in the human central nervous system [ 27 , 28 ]. Due to the non-toxicity of GABA, its simplicity, and its bi-functionality, we utilize it here as a modifying surface agent in the synthesis of ZnO NPs for controlling the size and morphology of the ZnO NPs.…”