Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function.

Area of Science:

• Immunology
• Hematology
• Microbiome-Host Interactions

Background:

• Rheumatoid arthritis (RA) elevates cardiovascular event risk due to abnormal platelet activity.
• Platelets originate from megakaryocytes, which develop from megakaryocyte erythrocyte progenitors (MEPs) in bone marrow.
• RA, lupus, and Sjögren's syndrome exhibit increased megakaryocyte expansion.

Purpose of the Study:

• To investigate the effect of propionate, a microbial short-chain fatty acid, on hematopoietic progenitors.
• To understand propionate's role in the collagen-induced inflammatory arthritis (CIA) model, given its previously observed protective effects.

Main Methods:

• Utilized the collagen-induced inflammatory arthritis (CIA) mouse model.
• Administered propionate treatment starting 21 days post-immunization (dpi).
• Analyzed bone marrow hematopoietic progenitor populations (MEPs), megakaryocytes, and platelet markers (CD61) using flow cytometry and RNA sequencing.

Main Results:

• Propionate treatment reduced MEP frequency in CIA and naive mice.
• Megakaryocyte numbers decreased, but CD61 expression (maturation marker) increased.
• Functional platelet analysis revealed heightened reactivity, supported by epigenetic modifications (histone acetylation/propionylation) and RNAseq data in Meg-01 cells.

Conclusions:

• Identified a novel nutritional pathway involving microbial short-chain fatty acids impacting platelet production and function.
• Propionate influences megakaryocyte development and platelet reactivity, offering potential therapeutic insights for RA-associated cardiovascular risks.