The microbiota has been shown to be critical for development of numerous physiological processes including maturation of the gastrointestinal (GI) tract and immune system. However, microbiota disturbances, particularly during early life, have been linked to disease development. Thus, mechanistically understanding how specific bacteria (including Bifidobacterium) influence host responses is key to the development of new therapies.
Lukas is investigating the effect of Bifidobacterium on intestinal health and in particular on intestinal epithelial cells. He is using transcriptional analysis (i.e. RNAseq) of host epithelium from in vivo models of homeostasis and pathological inflammation to pinpoint specific host signatures modulated by Bifidobacterium. The aim is to identify pathways involved in maintaining intestinal health that could be targeted for future therapies in the context of inflammatory diseases (e.g. Inflammatory Bowel Disease [IBD]).
Ian is also concentrating on intestinal inflammatory conditions, but with a specific focus on the microbial components that mediate these interactions. Bifidobacteria produce specific molecules (e.g. exopolysaccharide capsules) that positively impact epithelial integrity. Using a global bacterial genetic approach (i.e. Bifidobacterium random mutant library) and high throughput in vitro systems, using epithelium and immune cells, to identify further molecular and structural components that contribute to this protective effect with a view of utilising ‘anti-inflammatory’ Bifidobacteria as a therapy in IBD.
Zoe’s research is focused on the very early life window; there are links between disturbances of the mother’s microbiota during pregnancy and aberrant immune development in her baby. The current dogma that the foetal environment is sterile is being challenged by the presence of bacterial RNA/DNA in meconium, cord blood and the placenta. We are elucidating whether bacteria or bacterial components cross the placenta and at what stage, and how these ‘good bacteria’ impact immune development at various stages of pregnancy and early life. The aim is to promote infant health during pregnancy using beneficial bacteria.
Shannah is investigating the effects of Bifidobacterium on vaccine responses. The majority of vaccinations are administered in early life, a phase in which Bifidobacteria is important for immune development. Several clinical trials have shown that probiotic supplementation can improve vaccine immune responses, with these responses being dependent on the species/strain of bacteria administered. Using in vitro and in vivo models, Shannah aims to explore and characterise the immune mechanisms of how Bifidobacteria supplementation can enhance immune responses to vaccination, with a particular focus on vaccines against Typhoid Fever (caused by Salmonella Typhi), which has a global disease burden estimated at 11-20 million cases/year.
Lisa and Sarah are involved in a large clinical study exploring how ‘probiotic’ strategies in premature babies can help ‘restore’ the microbiota after disturbances due to a variety of factors (e.g. mode of delivery, antibiotics). Using NGS techniques, we are characterising preterm microbiota profiles and correlating this to metabolomics and immune readouts and clinical outcomes. Lisa is also working on identifying immune molecules as diagnostic markers for development of enteric infections.