Cited by 157Hematopoietic Stem Cell TransplantationGut microbiota and healthMesenchymal stem cell research

Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation

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Zeng, Xiangjun, Li, Xiaoqing, Li, Xia, Wei, Cong, Shi, Ce, Hu, Kejia, Kong, Delin, Luo, Qian +8 more·2023·Blood

Abstract

Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias, and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has recently been reported to affect hematopoiesis. However, there is currently limited empirical evidence explaining the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed a significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Furthermore, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated the FoxO signaling pathway, and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota composition and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.

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Authors
Zeng, X., Li, X., Li, X., Wei, C., Shi, C., Hu, K., Kong, D., Luo, Q., Xu, Y., Shan, W., Zhang, M., Shi, J., Feng, J., Han, Y., Huang, H., & Qian, P.
Affiliations
First Affiliated Hospital Zhejiang University (CN)
Corresponding author
  • Huang, He
  • Qian, Pengxu
Venue
Blood
Published
2023-04-06
Volume
141
Issue
14
Pages
1691-1707
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W4315926031
Cited by
157
References
57
Citations by year
2026: 44 · 2025: 41 · 2024: 52 · 2023: 20
FWCI
32.43
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Blood (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
Funders
  • National Natural Science Foundation of China (82070179, 81870080, 92268117, 91949115, 82130003, 82222003, 82161138028)
  • Zhejiang University
  • National Institutes of Health (1s10od030269-01, 1s10od026983-01)
  • National Key Research and Development Program of China (2018YFA0109300, 2022YFA1103500)
  • Natural Science Foundation of Zhejiang Province (LR19H080001, 82070179)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
hematopoietic stem cell aging, fecal microbiota transplantation, gut microbiota, hematopoiesis, lymphoid differentiation, myeloid differentiation, hematopoietic repopulation, inflammation, FoxO signaling, Lachnospiraceae, tryptophan metabolites
MeSH terms
Fecal Microbiota Transplantation, Animals, Cell Differentiation, Hematopoiesis, Hematopoietic Stem Cells, Inflammation, Mice

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