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. Gamma-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plants, animals and microorganisms 1,2. GABA is synthetized by a pyridocal-5′-phosphate (PLP)-dependent glutamate decarboxylase (GAD) enzyme by irreversible α-decarboxylation of l-glutamate and consummation of one cytoplasmic proton 1,2. GABA has several well-known physiological and psychological functions. Different studies highlighted that it is predominantly present in the brain where it acts as a major inhibitory neurotransmitter in the mammalian central nervous system (CNS) 1,2. Specifically, dysfunctions in GABA metabolism are involved in anxiety and depression 3-5. Furthermore, it is involved in the regulation of blood pressure and heart rate and plays a role in the perception of pain and anxiety 5,6. Other potential health benefits of GABA are control of growth hormone secretion, protection against glycerol-induced acute renal failure in rats and anti-proliferative activity 7. Recently, the term "psychobiotic" has been introduced to designate live bacterial strains, including lactobacilli and bifidobacteria, which are able to influence the CNS function 8. 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

Bifidobacteria are among the most abundant microorganisms inhabiting the intestine of humans and many animals. Within the genus Bifidobacterium, several beneficial effects have been attributed to strains belonging to the subspecies Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis, which are often found in infants and adults. The increasing numbers of sequenced genomes belonging to these two subspecies, and the availability of novel computational tools focused on predicting glycolytic abilities, with the aim of understanding the capabilities of degrading specific carbohydrates, allowed us to depict the potential glycoside hydrolases (GH) of these bacteria, with a focus on those GH profiles that differ in the two subspecies. We performed an in silico examination of 188 sequenced B. longum genomes and depicted the commonly present and strain-specific GHs and GH families among representatives of this species. Additionally, GH profiling, genome-based and 16S rRNA-based clustering analyses showed that the subspecies assignment of some strains does not properly match with their genetic background. Furthermore, the analysis of the potential GH component allowed the distinction of clear GH patterns. Some of the GH activities, and their link with the two subspecies under study, are further discussed. Overall, our in silico analysis poses some questions about the suitability of considering the GH activities of B. longum subsp. longum and B. longum subsp. infantis to gain insight into the characterization and classification of these two subspecies with probiotic interest.