Research

The Markey Lab was established in October 2021, and focuses on the intersection between the microbiome (and its metabolites) and the outcomes of cancer therapy – especially bone marrow transplantation and other immunotherapies. Our projects take clinical observational findings from studies of the intestinal microbiome (e.g. Markey et al, Blood 2020; Miltiadous et al, Blood 2022) through to mechanistic studies in mouse models. A number of observational studies have been performed supporting associations between the microbiome and transplant and/or immunotherapy outcome, but mechanistic data is currently lacking (e.g. Peled et al, NEJM 2020, Stein Thoeringer et al, Science 2020). Combining hypotheses generated from our clinical data with state-of-the-art immunology techniques in mouse model systems is important for addressing the current knowledge gaps in the field and supporting the design of microbiome-targeted interventions in future.

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We found that patients who went on to develop chronic GVHD were ‘missing’ the microbial short-chain fatty acids butyrate and propionate in circulation, compared with transplant patients who did not go on to develop chronic GVHD (Markey et al, 2020).
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We propose that the intestinal microbiota can influence immune cell development in the periphery via the production of metabolites which can act at distant sites (Andrlova et al, 2021)
Staphylococcal species present in the intestinal tract
We identified that a high relative abundance of Staphylococcal species present in the intestinal tract is linked with poor CD4 T cell recovery after transplantation. This may be due to circulating factors produced by Staphylococci that are detrimental to lymphopoiesis, and this requires further exploration in mouse models of transplantation (Miltiadous et al, Blood 2022).