Figure 1.

Microbiota and microbial metabolites can shape hematopoiesis and the immune response. Commensal microbes promote the maintenance of both hematopoietic stem cells (HSCs) and precursor myeloid cells. The absence of commensal microbes leads to defects in several innate immune cell populations, including neutrophils, monocytes, and macrophages. Feeding mice a diet rich in fiber changed the ratio of Firmicutes to Bacteroidetes and Bifidobacteriaceae. The presence of a complex intestinal microbiota specifically amplifies myelopoiesis in the bone marrow (BM). Dietary fiber is metabolized by gut microbiota, thereby increasing the levels of circulating short-chain fatty acids (SCFAs) and promoting the growing of myeloid precursors without affecting lymphoid progenitors in the BM. In the context of dysbiosis, the growth of pathogenic microbes acts as dormant bacterial reservoir that provides a source of persistent low-grade inflammation mediated by LPS and other pathogen-associated molecular patterns (PAMPs) that persistently stimulate hematopoietic stem progenitor cells via pathogen recognition receptors like TLR (TLR4, TLR7, and TLR9), leading to hematopoiesis inhibition. The LPS stimulation of TLR monocytes induces TNF-alpha secretion, and this persistent stimulation of HPSCs may further inhibit hematopoiesis via exhaustion.