Lundberg, Ludwig
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Research article2024Peer reviewedOpen access
Lundberg, Ludwig Ermann; Mishra, Punya Pallabi; Liu, Peidi; Forsberg, Manuel Mata; Sverremark-Ekstroem, Eva; Grompone, Gianfranco; Hakansson, Sebastian; Linninge, Caroline; Roos, Stefan
The aim of this study was to identify a Bifidobacterium strain that improves 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 co-cultivation. 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 transient receptor potential vanilloid 1 (TRPV1) and increased the expression of the immune development markers IL-6 and IL-1 beta in a peripheral blood mononuclear cell (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. IMPORTANCE By 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. Furthermore, 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.
Bifidobacterium longum; Limosilactobacillus reuteri; extracellular membrane vesicles; synergism; host interactions; randomized clinical trial; fiber utilization; bioactivity
Applied and Environmental Microbiology
2024, Volume: 90, number: 7Publisher: AMER SOC MICROBIOLOGY
Microbiology
DOI: https://doi.org/10.1128/aem.00247-24
https://res.slu.se/id/publ/131591