Oligosaccharide transport in probiotic bacteria of the gut microbiota.
The human gastrointestinal tract is colonized by a highly diverse and dynamic microbial community referred to as the gut microbiota. This bacterial consortium, which is established upon birth, co-develops with the host to form one of the most densely populated niche in nature. Probiotic members of this community, the majority of which are assigned into the Lactobacillus and Bifidobacterium genera, play an increasingly recognised role in maintaining and promoting human health by eliciting beneficial effects in e.g. pathogen exclusion, inflammatory bowel disease, allergies, obesity, as well as behaviour and brain function due to their interactions with the host and other members of the gut microbiota. These beneficial effects are intimately linked to diet, and are boosted by intake of mainly non-digestible oligosaccharides that selectively stimulate the proliferation of probiotics (prebiotics).
Currently, the determinants that govern the selective oligosaccharide utilization by probiotic bacteria are ill-understood. Efficient oligosaccharide uptake systems are, however, hypothesized to play a crucial role in supporting the adaptation to the highly competitive gut niche.
The aim of the project is to bring molecular insight into uptake of both dietary and host derived oligosaccharides by probiotic bacteria and evaluate the impact of oligosaccharide transport in modulation of the gut microbiota. The well characterized probiotic strain Lactobacillus acidophilus NCFM and bifidobacterial strains representing different metabolic niches will be investigated as to cover a broad range of oligosaccharides specificities. This will be achieved by:
Description of specificities, affinities and oligosaccharide ligand preferences of the solute binding proteins (SBPs) associated to ATP-binding cassette (ABC) transport systems from selected probiotic bacteria.
Identification of structural motifs defining the specificity/affinity of the above characterised SBPs using crystal structure determination.
Identification of the specificities of phosphoenolpyruvate-dependent phosphotransferase (PEP-PTS) transporters of L. acidophilus NCFM for a variety of disaccharides and plant glycosides.
Mapping of oligosaccharide transport, primarily in probiotic bacteria, by in silico comparative genomic and phylogenetic analyses, that integrate the experimental data from the project to assess the extent of occurrence and conservation of oligosaccharide uptake routes in other gut microbiota taxa.