Host-Microbiota Crosstalk

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.

We have an interest in non-communicable diseases, such as intestinal disorders and cancer, that may be linked to disturbances in the gut microbiota and dysregulated immune responses. We are keen to understand these conditions from the perspective of the microbe(s) and microbial factors that may mediate disease outcomes. For example, we have previously shown that specific molecules (e.g. exopolysaccharide capsules) produced by Bifidobacterium positively impact the gut barrier, which is often ‘leaky’ in inflammatory bowel disease. We are using a range of systems for this research, in vivo models that closely mimic human disease pathology, high throughput in vitro systems, and global bacterial genetic approaches, which will hopefully allow us to identify further molecular and structural components that contribute protective effects. The goal of these projects is to develop novel live biotherapeutics that can reduce disease-associated pathology and positively impact patient outcomes.

Previous work suggests that gut microbiota disturbances in the mother during pregnancy, and in the first 1000 days post birth have a magnified impact on infant health. Therefore, we are working to understand how certain microbes positively (or negatively) influence normal early life immune and metabolic development, including ‘boosting’ responses after e.g. vaccination. These studies involve a combination of clinical samples obtained from ongoing cohorts (PEARL [pregnant mothers and their infants] and BAMBI [preterm infants]), in vivo germ-free models, coupled with innovative sequencing and bioinformatic pipelines. If we can understand the influence of the microbiota on early life host, we may be able to develop new therapies to promote both maternal and infant health. Indeed, with BAMBI we have already been exploring how ‘probiotic’ strategies in premature babies can help ‘restore’ the microbiota, and how this relates to clinical outcomes like necrotising enterocolitis.