The interaction of the immune system with the environment has crucial implications in the context of autoimmunity that can be repurposed for the treatment of autoimmune diseases like multiple sclerosis and inflammatory bowel disease (IBD). Thus, we have been using engineered commensal microorganisms in order to target pathogenic pathways to treat these diseases.
One of these projects aimed to activate aryl hydrocarbon receptor (AhR), a tolerogenic transcription factor that is normally activated by small molecules provided by the diet and the gut flora. Indeed, using conditional knockout mice, transgenic mice expressing traceable proteins and single cell RNA seq, we demonstrated that EAE is ameliorated when mice are fed with novel bacteria engineered to produce AhR agonists and we are currently addressing the mechanisms of this findings. This project was developed in close collaboration with SYNLOGIC company.
Additionally, in a different project, we have targeted extracellular adenosine triphosphate known to be associated to intestinal inflammation and IBD pathology. We created synthetic yeast probiotics capable of sensing and at the same time producing apyrase in a proportional self-regulated fashion to degrade (Figure 2A). Treatment with these yeasts ameliorated experimental model of IBD (Figure 2B) and restored the gut microbiome (Figure 2C).
Figure 2 Self-Tunable Engineered Anti-Inflammatory Yeast Probiotics