Mining for the Next-Generation Microbiota Across the Gut–Brain Axis: A Case Study on the Translational Success of Bifidobacterium Longum APC1472

The identification of next-generation probiotics is a major challenge, as most bacterial strains have no major effect on gut–brain axis signaling. Translational studies have had limited success and clear mechanism of action are often lacking. Future studies should adapt mechanistic approaches to screen for bacterial strains and their metabolites, with specific activity and function across the gut–brain axis. Of particular interest is the pharmacological screening of the gut microbiota metabolome across key G-protein coupled receptors (GPCRs). We recently identified Bifidobacterium longum APC1472 able to attenuate signaling through the growth-hormone secretagogue receptor (GHSR-1a). Supplementation with this strain subsequently demonstrated a positive translational effect on glucose homeostasis and the stress-response in a preclinical mouse model and in a human intervention study. These recent findings demonstrate that classical pharmacological approaches can be utilized to screen the gut microbiota metabolome across key GPCR targets with pleiotropic action in the periphery and central nervous system.