Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives

Recent studies have shown that the gut microbiota plays a crucial role in the regulation of hematopoiesis due to the generation of a variety of metabolites. Metabolites generated by the gut microbiota, including Short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine N-oxide (TMAO), and bile acids, significantly affect the differentiation and function of hematopoietic stem and progenitor cells, as well as immune cell differentiation and activity. The effects of these metabolites are achieved through several signaling pathways, including Histone deacetylase (HDAC) inhibition by SCFAs, aryl hydrocarbon receptor (AHR)-dependent regulation of hematopoietic stem cell fate and myeloid commitment, and inflammasome signaling control by bile acids, among others. Of note, dysregulation of metabolite-mediated pathways has been shown to play a role in the development of several disorders such as anemia, hematologic or solid malignancies, Graft-vs.-host disease (GvHD), and cardiovascular diseases. In this review, we describe current findings on the mechanisms by which microbiota-derived metabolites influence hematopoietic processes and contribute to the development of hematological disorders, while also highlighting novel therapeutic approaches targeting microbiota–metabolite interactions.

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