Bifidobacterium longum subsp. longum BG-L47 boosts growth and activity of Limosilactobacillus reuteri DSM 17938 and its extracellular membrane vesicles

Ermann Lundberg, L.; Pallabi Mishra, P.; Liu, P.; Forsberg, M. M.; Sverremark-Ekström, E.; Grompone, G.; Hakansson, S.; Linninge, C.; Roos, S.

doi:10.1101/2024.02.12.579962

bioRxiv · 10.1101/2024.02.12.579962

Bifidobacterium longum subsp. longum BG-L47 boosts growth and activity of Limosilactobacillus reuteri DSM 17938 and its extracellular membrane vesicles

Ermann Lundberg, L.·Pallabi Mishra, P.·Liu, P.·Forsberg, M. M.·Sverremark-Ekström, E.·Grompone, G.·Hakansson, S.·Linninge, C.·Roos, S.

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Abstract

The aim was to identify a Bifidobacterium strain that improved the performance of Limosilactobacillus reuteri DSM 17938. Initial tests showed that Bifidobacterium longum subsp. longum strains boosted the growth of DSM 17938 during in 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. longum subsp. longum cells boosted the bioactivity of extracellular membrane vesicles (MV) produced by L. reuteri DSM 17938 during cocultivation. Secreted 5 nucleotidase (5NT), 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-1{beta} 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. longum subsp. longum BG-L47 has favorable physiological properties, can boost the in vitro activity of L. reuteri DSM 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 of Bifidobacterium longum subsp. longum strains 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 strain Limosilactobacillus reuteri DSM 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.

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Ermann Lundberg, L., Pallabi Mishra, P., Liu, P., Forsberg, M. M., Sverremark-Ekström, E., Grompone, G., Hakansson, S., Linninge, C., Roos, S.. 2024-02-14. Bifidobacterium longum subsp. longum BG-L47 boosts growth and activity of Limosilactobacillus reuteri DSM 17938 and its extracellular membrane vesicles. https://doi.org/10.1101/2024.02.12.579962

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