Research profile

The gut microbiome engages in constant interactions with the immune system, laying fundamentals for what we perceive as health or disease. The microbiome acts locally in the gut and distally in other organs (for example, the lungs or the brain). These wide‑ranging effects are achieved, at least in part, through microbial metabolites released into circulation. Prime examples are short‑chain fatty acids (SCFAs), shown to protect against various conditions. However, SCFAs, along with a handful of other compounds, constitute only a small fraction of microbial products known for their immunomodulatory activity. This underlines an urgent need for discoveries of new metabolites, defining their mechanisms of action and testing them in different disease settings. Our research program aims to identify immunosuppressive metabolites active in the lungs and the brain, explain their mechanisms of action, and tailor them toward the formulation of therapeutics against acute respiratory distress syndrome and multiple sclerosis. We believe this strategy may pave the way to harnessing microbial metabolites for human health benefits.

Current research activities

• Screening metabolite libraries for their immunosuppressive potential using primary lung/brain cell culture methods
• Chemical optimization of therapeutic leads
• Unravelling their mechanisms of action via RNA sequencing
• Testing efficacy of metabolite regimens to reduce inflammation in mouse models of acute respiratory distress syndrome and multiple sclerosis

Selected publications

Davis, J., Wypych, TP. (2021), Cellular and functional heterogeneity of the airway epithelium, Mucosal Immunol. https://doi.org/10.1038/s41385-020-00370-7

Wypych, TP., Pattaroni, C., Perdijk, O., Yap, C., Trompette, A., Anderson, D., Creek, D., Harris, NL and Marsland, BJ* (2021). Microbial metabolism of L-tyrosine protects against allergic airway inflammation. Nat Immunol 22, 279–286. https://doi.org/10.1038/s41590-020-00856

Wypych, TP., Wickramasinghe, LK., Marsland, BJ. (2019). The influence of the microbiome on respiratory health. Nat Immunol 20, 1279-1290. https://doi.org/10.1038/s41590-019-0451-9

Wypych, TP. & Marsland, BJ. (2018). Antibiotics as instigators of microbial dysbiosis: implications for asthma and allergy. Trends Immunol 39, 697-711, Doi: https://doi.org/10.1016/j.it.2018.02.008

Wypych, TP., Marsland, BJ., Ubags, NDJ. (2017). The Impact of Diet on Immunity and Respiratory Diseases. Ann Am Thorac Soc. 14(Supplement_5):S339-S347. Doi: https://doi.org/10.1513/AnnalsATS.201703-255AW

Wypych, TP. & Marsland, BJ. (2017). Diet Hypotheses in Light of the Microbiota Revolution: New Perspectives. Nutrients 9(6), 537. Doi: https://doi.org/10.3390/nu9060537