Journal Article

Microbiota-derived lactate promotes hematopoiesis and erythropoiesis by inducing stem cell factor production from leptin receptor+ niche cells

Lee, Yong-Soo, Eunju, O., Kweon, Mi-Na, Kim, Seungil, Lee, Su-Hyun, Seo, Sang-Uk, Kim, Tae-Young, Kim, Kwang Soon, Zhou, Bo O., Kim, Yeji

2021

Overview

Although functional interplay between intestinal microbiota and distant sites beyond the gut has been identified, the influence of microbiota-derived metabolites on hematopoietic stem cells (HSCs) remains unclear. This study investigated the role of microbiota-derived lactate in hematopoiesis using mice deficient in G-protein-coupled receptor (Gpr) 81 (Gpr81 − /− ), an established lactate receptor. We detected significant depletion of total HSCs in the bone marrow (BM) of Gpr81 −/− mice compared with heterogenic (Gpr81 +/− ) mice in a steady state. Notably, the expression levels of stem cell factor (SCF), which is required for the proliferation of HSCs, decreased significantly in leptin receptor-expressing (LepR + ) mesenchymal stromal cells (MSCs) around the sinusoidal vessels of the BM from Gpr81 −/− mice compared with Gpr81 +/− mice. Hematopoietic recovery and activation of BM niche cells after irradiation or busulfan treatment also required Gpr81 signals. Oral administration of lactic acid-producing bacteria (LAB) activated SCF secretion from LepR + BM MSCs and subsequently accelerated hematopoiesis and erythropoiesis. Most importantly, LAB feeding accelerated the self-renewal of HSCs in germ-free mice. These results suggest that microbiota-derived lactate stimulates SCF secretion by LepR + BM MSCs and subsequently activates hematopoiesis and erythropoiesis in a Gpr81-dependent manner. Blood cell formation: Support from gut bacteria Lactic acid produced by microbes in the gut has been implicated in supporting the production of blood cells, suggesting oral administration of lactic acid-producing bacteria might be useful for treating blood disorders, including anemia. Researchers in South Korea and China, led by Mi-Na Kweon at the University of Ulsan in Seoul, explored the significance of lactic acid using mice deficient in the gene for a protein receptor that allows lactic acid to influence various cellular processes. Without the benefit of this receptor the levels of blood cell-forming stem cells in bone marrow were reduced. The normal effect of lactic acid was linked to production of a protein called stem cell factor in specific cells. Oral administration of lactic acid-producing bacteria restored blood cell formation, indicating its therapeutic potential.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,생화학분자생물학회
• Subject: 13/31 / 13/51 / 631/250 / 692/308/2171 / Acids / Animal models / Animals / Bacteria / Biomarkers / Biomedical and Life Sciences / Biomedicine / Blood / Blood cells / Bone marrow / Bone Marrow - metabolism / Bone Marrow - radiation effects / Bone Marrow Cells - cytology / Bone Marrow Cells - metabolism / Bone Marrow Cells - radiation effects / Busulfan / Cell activation / Cell proliferation / Cell self-renewal / Digestive system / Erythropoiesis / G protein-coupled receptors / Gastrointestinal tract / Germfree / Hematological diseases / Hematopoiesis / Hematopoietic Stem Cells / Host Microbial Interactions / Immunophenotyping / Intestinal microflora / Lactic acid / Lactic Acid - metabolism / Medical Biochemistry / Mesenchyme / Mice / Mice, Knockout / Microbiota / Models, Biological / Molecular Medicine / Oral administration / Probiotics / Proteins / Radiation / Receptors, Leptin - metabolism / Secretion / Signal Transduction / Stem cell factor / Stem Cell Factor - metabolism / Stem Cell Niche / Stem cell transplantation / Stem Cells / Stromal cells / 생화학