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.

More information: https://nenckimicrobiome.nencki.edu.pl/

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

Ciuba K, Piotrowska A, Chaudhury D, Dehingia B, Du.ski E, Behr R, Soroczy.ska K, Czystowska-Ku.micz M, Abbas M, Bulanda E, Gawlik-Zawi.lak S, Pietrzak S, Figiel I, W.odarczyk J, Verkhratsky A, Niedba.a M, Kaspera W, Wypych T, Wilczy.ski B, P.kowska A. Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution. Cell Stem Cell. 2025 Jan 29:S1934-5909(24)00458-2. doi: 10.1016/j.stem.2024.12.011. Epub ahead of print. PMID: 39909043.

Perdijk, O*, Butler, A, Macowan, M., Chatzis, R, Bulanda, E. , Grant, RD, Harris, NL., Wypych, TP*# and Marsland, BJ*#. Indole-3-propionic acid production in early life prevents exaggerated allergic inflammation in adulthood, Immunity, 2024 Jul 6:S1074-7613(24)00316-9. doi: 10.1016/j.immuni.2024.06.010. pub ahead of print. PMID: 39013465 *corresponding authors, #senior authors

Wolska, M.; Wypych, TP*.; Rodriguez-Viso, P. The Influence of Premature Birth on the Development of Pulmonary Diseases: Focus on the Microbiome. Metabolites 2024, 14, 382. https://doi.org/10.3390/metabo14070382 *corresponding author

Osial M, Wilczewski S, Godlewska U, Skorczewska K, Hilus J, Szulc J, Roszkiewicz A, D.browska A, Moazzami Goudarzi Z, Lewandowski K, Wypych TP, Nguyen PT, Sumara G, Giersig M. Incorporation of Nanostructural Hydroxyapatite and Curcumin Extract from Curcuma longa L. Rhizome into Polylactide to Obtain Green Composite. Polymers (Basel). 2024 Jul 30;16(15):2169. doi: 10.3390/polym16152169. PMID: 39125199; PMCID: PMC11315054.

Losol P, Wolska M, Wypych TP, Yao L, O’Mahony L, Sokolowska M. A cross talk between microbial metabolites and host immunity: Its relevance for allergic diseases. Clin Transl Allergy. 2024 Feb;14(2):e12339. doi: 10.1002/clt2.12339. PMID: 38342758; PMCID: PMC10859320.

Latorre D, Monticelli S, Wypych TP, Aschenbrenner D, Notarbartolo S. Editorial: T cell specificity and cross-reactivity – implications in physiology and pathology. Front Immunol. 2024 Feb 28;15:1385415. doi: 10.3389/fimmu.2024.1385415. PMID: 38481997; PMCID: PMC10933105.

Bulanda E, Wypych TP* Microbes, antibodies, and breastfeeding as the trans-generational axis of microbiota maturation. Allergy 2023 Aug;78(8):2318-2320. doi: 10.1111/all.15713. Epub 2023 Mar 23. *corresponding author

Godlewska U, Bulanda E, Wypych TP* . Bile acids in immunity: Bidirectional mediators between the host and the microbiota. Front Immunol. 2022 Aug 16;13:949033. doi: 10.3389/fimmu.2022.949033. PMID: 36052074; PMCID: PMC9425027. *corresponding author

Bulanda E, Wypych TP*. Bypassing the Gut-Lung Axis via Microbial Metabolites: Implications for Chronic Respiratory Diseases. Front Microbiol. 2022 May 3;13:857418. doi: 10.3389/fmicb.2022.857418. PMID: 35591998; PMCID: PMC9113535. *corresponding author

Gonzalez-Loyola A, Bovay E, Kim J, Lozano TW, Sabine A, Renevey F, Arroz-Madeira S, Rapin A, Wypych TP, Rota G, Durot S, Velin D, Marsland B, Guarda G, Delorenzi M, Zamboni N, Luther SA, Petrova TV. FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure. Sci Adv. 2021 Jul 16;7(29):eabf4335. doi: 10.1126/sciadv.abf4335. PMID: 34272244; PMCID: PMC8284898.

Davis JD, Wypych TP*. Cellular and functional heterogeneity of the airway epithelium. Mucosal Immunol. 2021 Sep;14(5):978-990. doi: 10.1038/s41385-020-00370-7. Epub 2021 Feb 19. Erratum in: Mucosal Immunol. 2022 Mar;15(3):528. PMID: 33608655; PMCID: PMC7893625. *corresponding author

Wypych TP*, Pattaroni C, Perdijk O, Yap C, Trompette A, Anderson D, Creek DJ, Harris NL, Marsland BJ*. Microbial metabolism of L-tyrosine protects against allergic airway inflammation. Nat Immunol. 2021 Mar;22(3):279-286. doi: 10.1038/s41590-020-00856-3. Epub 2021 Jan 25. PMID: 33495652. *corresponding author

Wypych TP*, Wickramasinghe LC, Marsland BJ*. The influence of the microbiome on respiratory health. Nat Immunol. 2019 Oct;20(10):1279-1290. doi: 10.1038/s41590-019-0451-9. Epub 2019 Sep 9. PMID: 31501577. *corresponding author

Wypych TP*, Marsland BJ*. Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and Allergy. Trends Immunol. 2018 Sep;39(9):697-711. doi: 10.1016/j.it.2018.02.008. Epub 2018 Apr 11. PMID: 29655522. *corresponding author

Wypych TP, Marsland BJ, Ubags NDJ. The Impact of Diet on Immunity and Respiratory Diseases. Ann Am Thorac Soc. 2017 Nov;14(Supplement_5):S339-S347. doi: 10.1513/AnnalsATS.201703-255AW. PMID: 29161092.

Wypych TP*, Marzi R, Wu GF, Lanzavecchia A, Sallusto F*. Role of B cells in TH cell responses in a mouse model of asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1395-1410. doi: 10.1016/j.jaci.2017.09.001. Epub 2017 Sep 7. PMID: 28889953; PMCID: PMC6594185. *corresponding author

Wypych TP*, Marsland BJ. Diet Hypotheses in Light of the Microbiota Revolution: New Perspectives. Nutrients. 2017 May 24;9(6):537. doi: 10.3390/nu9060537. PMID: 28538698; PMCID: PMC5490516. *corresponding author

den Dunnen J, Vogelpoel LT, Wypych T, Muller FJ, de Boer L, Kuijpers TW, Zaat SA, Kapsenberg ML, de Jong EC. IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and FcƒÁRIIa in human dendritic cells. Blood. 2012 Jul 5;120(1):112-21. doi: 10.1182/blood-2011-12-399931. Epub 2012 May 30. PMID: 22