In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors

ABSTRACT

Fecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.

KEYWORDS:

• Bacteriotherapy
• dysbiosis
• fecal microbiota transplantation
• gut microbiota
• next-generation probiotics

Acknowledgments

We acknowledge DNA Sequencing and Genomics Laboratory, Institute of Biotechnology, University of Helsinki for 16S rRNA gene amplicon sequencing. We thank Vita Laboratories Inc. for the possibility to use the MALDI-TOF MS equipment for this study. We thank Sari Laakkonen at the Laboratory Animal Center of the University of Helsinki for performing oral gavage in mice. We thank Eric Schaedig at the Biosciences Center of the National Renewable Energy Laboratory (CO, United States) for guidance in the design of RNA extraction protocol. Finally, we thank Sofia Wiksten at the University of Helsinki for assistance in the selective cultivation. Open access funded by Helsinki University Library.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2229944

Additional information

Funding

The study was supported by the Novo Nordisk Foundation [Grant no. 34840], Sigrid Jusélius and Paulo Foundations (Senior Researcher’s Grants to RS), Academy of Finland [Grant No. 323156 to RS], and Väisälä Fund [Grant to AR], Finland.