Abstract
Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut–brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains allowed identifying two high GABA producers, i.e. B. adolescentis PRL2019 and B. adolescentis HD17T2H, which were employed in an in vivo trial in rats. Feeding Groningen rats with a supplementation of B. adolescentis strains, confirmed the ability of these microorganisms to stimulate the in vivo production of GABA highlighting their potential implication in gut–brain axis interactions.
Highlights
Gamma-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plants, animals and microorganisms[1,2]
The dissected proteome of 1,022 bifidobacterial strains retrieved from the genomic National Center for Biotechnology Information (NCBI) database as well as our bifidobacterial genome database (Table S1), revealed that 81 strains encode for both glutamate decarboxylase (GadB) and GadC, encompassing seven different species, i.e., B. adolescentis, Bifidobacterium angulatum, B. dentium, Bifidobacterium merycicum, Bifidobacterium moukalabense, Bifidobacterium ruminantium and Bifidobacterium samirii (Table S3)
Based on the sequence identity values obtained between the identified protein sequences, we observed a higher conservation among members of the B. adolescentis phylogenetic group, while lower values of identity were found in B. angulatum, B. merycicum and B. samirii taxa, which reflect their belonging to other bifidobacterial phylogenetic groups[14,15] (Fig. 1a)
Summary
Gamma-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plants, animals and microorganisms[1,2]. There are several compounds produced by these bacteria, such as proteins, peptides and components of cell wall that are potential mediators between bacteria and their hosts Neurotransmitters, such as GABA, represent an example of neuroactive molecules. Produced by psychobiotics and members of the human gut microbiota that have been found to modulate neural signals which affect neurological and psychiatric parameters, as well as sleep, appetite, mood and c ognition[8] It has been found the presence of gad genes, predicted to encode for glutamate decarboxylase or glutamic acid decarboxylase, in the genomes of Lactic Acid Bacteria (LAB) and bifidobacteria that are supposed to be responsible of the GABA p roduction[5,9,10,11,12]. The screening of metagenomic datasets of clinical population and rat models of depression and anxiety revealed an intriguing association/correlation between B. adolescentis load and these mental disorders
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