Examination of the effects of the intestinal microbiome on metabolism and systemic inflammation using integrated molecular imaging technologies

The gut microbiome is important in host health, nutrition and pharmaceutical metabolism and absorption. Numerous studies have highlighted the positive role of the microbiome but it is clear that the interaction between gut microbes and the immune system can contribute to induction and exacerbation of inflammatory pathologies. Perturbation in gut microbiome composition, triggered by insults such as gastroenteritis or antibiotic treatment, can result in an immune response that may be targeted at specific microbial antigens but which also attacks host gut tissues. The mechanisms behind systemic inflammation in many diseases remain to be discovered but the central role of the intestine and the significant remission in symptoms post-manipulation of the intestinal microbiota point towards a significant gut microbiota input into disease.

We have recently applied mass spectrometry imaging (MSI) approaches to investigate links between the gut microbiome and host physiology, identifying microbial products that are produced in the gut and that interact with host tissues systemically. These approaches have the potential to reveal the molecular basis of the communication between the gut microbiota and the host immune system. We have also demonstrated through mass spectrometry imaging that we can detect the absorption profile of a range of therapeutics, simultaneously, across the villi axis.

Using state of the art techniques including imaging mass cytometry (IMC - murine specific panel allowing >40-plex immunohistochemistry) and mass spectrometry imaging (MSI) we can for the first-time link metabolism with cell phenotyping, pathway analysis & function. This will allow us to study the interplay between microbiome and inflammation on healthy metabolism physiology. This puts us in a unique position to be able to study, in unparalleled resolution, the effect of the microbiome on metabolism and systemic inflammation.

Start date: 1 October 2019