Prebiotics and the gut–bone marrow axis: potential remodeling of the hematopoietic/leukemic stem cell niche via short-chain fatty acids and AhR signaling
6 affiliations
- 1Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China
- 2Department of Clinical Laboratory, Jiuzhaigou County People’s Hospital
- 3Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Emergency Department
- 4Department of Clinical Laboratory, The Third Hospital of Mianyang
- 5Department of Clinical Laboratory, People’s Hospital of Mianyang
- 6Department of Clinical Laboratory, Sichuan Taikang Hospital
Abstract
Gut microbiota metabolites, such as short-chain fatty acids (SCFAs) and tryptophan-derived indole ligands of the aryl hydrocarbon receptor (AhR), can enter the circulation and modulate the bone marrow microenvironment, influencing hematopoietic and immune homeostasis. Recent studies suggest that these metabolites may reach the bone marrow and affect the hematopoietic and leukemic stem cell (HSC/LSC) niche. Increasing evidence indicates that the gut microbiome influences bone marrow hematopoiesis through metabolic products and host signaling networks, a bidirectional communication described as the gut–bone marrow axis (GBMA). Along this axis, prebiotic-associated SCFAs and tryptophan–indole/AhR ligands may penetrate the bone marrow microenvironment. However, several specific questions remain unresolved: whether defined prebiotic interventions consistently alter circulating and bone marrow-accessible levels of SCFAs and indole/AhR ligands; which bone marrow cell populations these metabolites target and through what mechanisms; whether they differentially affect normal HSCs and LSCs, including across leukemia subtypes; and whether these changes translate into clinically meaningful outcomes. This review synthesizes evidence on how prebiotic-associated SCFAs and indole/AhR signaling may affect HSC and LSC fate through epigenetic regulation, receptor signaling, and bone marrow niche responses. It also evaluates the current translational evidence and outlines priorities for mechanistic studies and prospective clinical trials.
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BibTeX
@article{wang2026prebiotics,
title = {{Prebiotics and the gut–bone marrow axis: potential remodeling of the hematopoietic/leukemic stem cell niche via short-chain fatty acids and AhR signaling}},
author = {Zexin Wang and Qiang Yang and Haiping Guo and Zerui Yang and Yang Yang and Meng Peng and Miao Liu and Liwen Cao and Tao Huang and Yuanyuan Li and Jiawei Zeng},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1913887},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1913887/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prebiotics and the gut–bone marrow axis: potential remodeling of the hematopoietic/leukemic stem cell niche via short-chain fatty acids and AhR signaling
AU - Zexin Wang
AU - Qiang Yang
AU - Haiping Guo
AU - Zerui Yang
AU - Yang Yang
AU - Meng Peng
AU - Miao Liu
AU - Liwen Cao
AU - Tao Huang
AU - Yuanyuan Li
AU - Jiawei Zeng
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1913887
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1913887/full
AB - Gut microbiota metabolites, such as short-chain fatty acids (SCFAs) and tryptophan-derived indole ligands of the aryl hydrocarbon receptor (AhR), can enter the circulation and modulate the bone marrow microenvironment, influencing hematopoietic and immune homeostasis. Recent studies suggest that these metabolites may reach the bone marrow and affect the hematopoietic and leukemic stem cell (HSC/LSC) niche. Increasing evidence indicates that the gut microbiome influences bone marrow hematopoiesis through metabolic products and host signaling networks, a bidirectional communication described as the gut–bone marrow axis (GBMA). Along this axis, prebiotic-associated SCFAs and tryptophan–indole/AhR ligands may penetrate the bone marrow microenvironment. However, several specific questions remain unresolved: whether defined prebiotic interventions consistently alter circulating and bone marrow-accessible levels of SCFAs and indole/AhR ligands; which bone marrow cell populations these metabolites target and through what mechanisms; whether they differentially affect normal HSCs and LSCs, including across leukemia subtypes; and whether these changes translate into clinically meaningful outcomes. This review synthesizes evidence on how prebiotic-associated SCFAs and indole/AhR signaling may affect HSC and LSC fate through epigenetic regulation, receptor signaling, and bone marrow niche responses. It also evaluates the current translational evidence and outlines priorities for mechanistic studies and prospective clinical trials.
SN - 1664-3224
ER -