Mouse intestinal microbiome modulation by oral administration of a GABA-producing Bifidobacterium adolescentis strain

Abstract

ABSTRACT Emerging evidence suggests that gut microbes can significantly contribute to central nervous system (CNS) well functioning through several gut microbiome-brain signaling mechanisms, among which the production of neurotransmitters by commensal microbes is very relevant. Hence, there is increasing interest in developing probiotics with capacity to deliver, locally within the gut ecosystem, neurotransmitters. The gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS, and its disbalance has been associated with numerous disorders, including depression or anxiety. Furthermore, some commensal gut microorganisms are capable to produce GABA from its precursor, glutamate, whose concentration is generally higher in patients from disorders such as fibromyalgia, chronic fatigue, and pain. Therefore, we postulate that the administration of GABA-producing probiotic microorganisms may contribute to ameliorate conditions related to high glutamate/low GABA concentrations. In a prior work, we demonstrated a significant reduction of serum glutamate concentration in mice following 2-week administration of a GABA-producing Bifidobacterium adolescentis strain, IPLA60004. Herein, we further investigate the impact that the probiotic administration may have on the gut microbiome composition and metabolism. Remarkably, the gut microbiota modulation observed was different in animals receiving the GABA-producing strain, IPLA60004, as compared to animals receiving a closely related strain without GABA-producing ability. Genera of commensal and beneficial microorganisms, including Lactobacillus, Roseburia, and novel Lachnospiraceae genera, reached significantly higher representation at late intervention points in the fecal microbiota of animals receiving the GABA-producing strain, suggesting that some of the physiological effects of the probiotic administration may be linked to specific gut modulation effects. IMPORTANCE The gut microbiome-brain communication signaling has emerged in recent years as a novel target for intervention with the potential to ameliorate some conditions associated with the central nervous system. Hence, probiotics with capacity to produce neurotransmitters, for instance, have come up as appealing alternatives to treat disorders associated with disbalanced neurotransmitters. Herein, we further deep into the effects of administering a gamma-aminobutyric acid (GABA)-producing Bifidobacterium strain, previously demonstrated to contribute to reduce serum glutamate levels, in the gut microbiome composition and metabolic activity in a mouse model. Our results demonstrate that the GABA-producing strain administration results in a specific pattern of gut microbiota modulation, different from the one observed in animals receiving non-GABA-producing strains. This opens new avenues to delineate the specific mechanisms by which IPLA60004 administration contributes to reducing serum glutamate levels and to ascertain whether this effect could exert health benefits in patients of diseases associated with high-glutamate serum concentrations.

Keywords

• B. adolescentis
• GABA
• microbiome modulation