A holistic study of the effect of the murine microbiome on metabolism and systemic inflammation using integrated molecular imaging technologies

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Studentship strategic priority area: Basic Bioscience Underpinning HeathKeywords: Molecular Imaging Microbiome Inflammation Abstract: The gut microbiome is essential to host health, nutritional 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 modulation of metabolism and 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. Understanding this relationship may allow intervention across a range of animal diseases, where similar to human disease, the gut microbiome exerts effects far beyond the intestine. 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. Indeed our recent work employing this approach is the first to describe direct molecular inter-kingdom communication between prokaryotes and the mammalian brain leading to inhibition of brain cell function. This approach has enabled us to do something others cannot, ascribe a mechanistic function to newly identified products from the gut microbiome. In a parallel collaboration, again using MSI, we have also demonstrated that we can detect the absorption profile of a range of therapeutics, simultaneously, across the villi axis. With our imaging mass cytometry (IMC) capability, (murine specific panel allowing >40-plex immunohistochemistry) 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 and the effect on healthy metabolism physiology. Combined, these three research streams have now put us in a unique position to study, in unparalleled resolution, the effect of the microbiome on metabolism and systemic inflammation.