Microbiota-derived bile acid ameliorates lung inflammation through metabolic rewiring of alveolar macrophages
Speaker: Dr Tomasz Wypych, Nencki Institute of Experimental Biology, Warsaw
Talk: Microbiota-derived bile acid ameliorates lung inflammation through metabolic rewiring of alveolar macrophages
Time: 06.12.2024, 9:00 am
Venue: Intercollegiate Faculty of Biotechnology, Abrahama 58, hall 042B
The gut microbiota profoundly shapes our immunity, acting locally in the gut and distally in other organs, such as the lungs . These wide ranging effects are achieved, at least in part, through microbial metabolites released into circulation. Secondary bile acids, which are derived from the transformation of host-derived bile acids by the gut microbiota, have recently emerged as potent anti-inflammatory mediators in the intestine, affecting the differentiation of CD4+ T cells and the function of dendritic cells. Despite this, it remains unclear which bile acid species display the most pronounced effects and what mechanisms are implicated.To fill in this gap, we comprehensively screened a library of primary, conjugated, and secondary bile acids for their ability to suppress the inflammatory response in the airways. We identified one particular species belonging to secondary bile acids (hereinafter referred to as “the Metabolite X” due to pending patent application), which profoundly inhibited the inflammatory response in the lungs. Met. X acted through Sphingosine-1-phosphate receptor 2 (S1PR2) to induce metabolic rewiring of alveolar macrophages, dampening the production of chemokines (predominantly CXCL9, CXCL10, and CXCL11), and reactive oxygen species. Collectively, our data identify the microbiota-dependent secondary bile acid that ameliorates lung inflammation through S1PR2-dependent metabolic rewiring of alveolar macrophages.
Dr inż. Tomasz Wypych is the head of the Host-Microbiota Laboratory at the Nencki Institute of Experimental Biology. He obtained his PhD in 2016 from the University of Bern, under the supervision of Prof. Federica Sallusto. His PhD thesis concerned the role of B cells as antigen presenting cells in asthma. He then completed his postdoctoral training at Lausanne University Hospital and Monash University focusing on the cross-talk between host cells and the microbiota in shaping susceptibility to asthma. His current research revolves around the effects of microbial metabolites on immunity. Major scientific achievements of Dr. Wypych include publication of 17 peer-reviewed articles in the area of immunology and microbiome. He is also an author of 2 patent applications and secured funding for 5 major grants (IDEAS grant, NHMRC Australia; Sonata grant, NCN Poland; OPUS grant, NCN Poland, First Team FENG grant, FNP Poland and OPUS+LAP grant, NCN, Poland and SNSF, Switzerland). Finally, he was awarded the Scholarship from the Ministry of Science and Education for Outstanding Young Scientists.