Beyond the Gut: Microbiota-Derived Bile Acids in Tissue Immunity and Inflammation

We are pleased to announce that Prof. Tomasz Wypych, from Nencki Institute of Experimental Biology PAS, Poland, will join 13th Worls Congress on Targeting Microbiota - ISM 2026 as a speaker.

The gut microbiota produces a remarkable diversity of bioactive molecules, many of which remain functionally unexplored. These metabolites provide a chemical link between microbes and distant organs and may represent an untapped source of new therapeutic strategies. Among them, microbiota-derived bile acids are emerging as particularly powerful regulators of host immunity.

In this talk, I will discuss our work uncovering the unexpected reach of these molecules across tissues. Through screening of microbiota-associated bile acids, we identified isolithocholic acid (isoLCA) as a particularly potent immunomodulatory metabolite. Remarkably, its activity extends across anatomically distant organs and across both immune and structural compartments. In the lung, isoLCA reprograms the immunometabolism of alveolar macrophages and pulmonary fibroblasts, limiting allergic airway inflammation and improving lung function. In the central nervous system, it acts primarily on astrocytes, reshaping their inflammatory state and, in turn, their communication with microglia and neurons, promoting neuronal homeostasis and protecting against neuroinflammation in vivo. These findings illustrate how a single microbial metabolite can engage fundamentally different tissue-resident cell populations to restrain inflammation across organs.

This biology also opens therapeutic opportunities. Beyond direct administration of immunomodulatory metabolites, we show that beneficial bile acid pathways can be restored through rational manipulation of the microbiota. Together, our work positions microbiota-derived bile acids as a largely untapped class of systemic immunoregulatory molecules and a promising starting point for new approaches to inflammatory disease.