Bifidobacterium longumsubsp. longumBG-L47 boosts growth and activity ofLimosilactobacillus reuteriDSM 17938 and its extracellular membrane vesicles

Abstract

AbstractThe aim was to identify aBifidobacteriumstrain that improved the performance ofLimosilactobacillus reuteriDSM 17938. Initial tests showed thatBifidobacterium longumsubsp.longumstrains boosted the growth of DSM 17938 duringin vivo-like conditions. Further characterization revealed that one of the strains, BG-L47, had better bile and acid tolerance compared to BG-L48, as well as mucus adhesion compared to both BG-L48 and the control strain BB536. BG-L47 also had the capacity to metabolize a broad range of carbohydrates and sugar alcohols. Mapping of glycoside hydrolase (GH) genes of BG-L47 and BB536 revealed many GHs associated with plant-fiber utilization. However, BG-L47 had a broader phenotypic fiber utilization capacity. In addition,B. longumsubsp.longumcells boosted the bioactivity of extracellular membrane vesicles (MV) produced byL. reuteriDSM 17938 during cocultivation. Secreted 5’ nucleotidase (5’NT), an enzyme that converts AMP into the signal molecule adenosine, was increased in MV boosted by BG-L47. The MV exerted an improved antagonistic effect on the pain receptor TRPV1 and increased the expression of the immune development markers IL-6 and IL-1ß in a PBMC model. Finally, the safety of BG-L47 was evaluated both by genome safety assessment and in a human safety study. Microbiota analysis showed that the treatment did not induce significant changes in the composition. In conclusion,B. longumsubsp.longumBG-L47 has favorable physiological properties, can boost thein vitroactivity ofL. reuteriDSM 17938, and is safe for consumption, making it a candidate for further evaluation in probiotic studies.ImportanceBy using probiotics that contain a combination of strains with synergistic properties, the likelihood of achieving beneficial interactions with the host can increase. In this study, we first performed a broad screening ofBifidobacterium longumsubsp.longumstrains in terms of synergistic potential and physiological properties. We identified a superior strain, BG-L47, with favorable characteristics and potential to boost the activity of the known probiotic strainLimosilactobacillus reuteriDSM 17938. Further, we demonstrated that BG-L47 is safe for consumption in a human randomized clinical study and by performing a genome safety assessment. This work illustrates that bacteria-bacteria interactions differ at the strain level and further provides a strategy for finding and selecting companion strains of probiotics.