David Esteban, Associate Professor of Biology, received one of nine research grants made by the Patient-Led Research Collaborative in support of his project entitled “Microbial metabolites as disease-modifying factors in Long-COVID.” The Patient-Led Research Collaborative supports research into Long COVID and associated conditions and also advocates for policies that enable patients.

David’s research will investigate the production of, and response to, microbially derived AhR ligands in the microbiomes of people with Long COVID. Under healthy conditions, gut microbes produce an abundance of small molecules from tryptophan, which enter cells and activate the aryl hydrocarbon receptor (AhR). AhR induces expression of genes that limit inflammation and maintain the gut barrier. These ligands can also cross into the bloodstream and activate AhR distally to control inflammation and other processes. Under certain disease conditions, an altered microbial community is less able to produce AhR ligands from tryptophan. AhR therefore does not maintain the gut barrier and does not help control inflammation, while pro-inflammatory bacterial components are allowed to cross into the bloodstream. Due to the established connection between the gut microbiome, brain, and immune system, David’s foundational research will be critical in understanding the basis of neuroinflammation, immune dysfunction, and gastrointestinal homeostasis, in post-infectious chronic diseases. This study expands his ongoing research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) allowing comparison of these closely related diseases.