Gut microbiota disturbance disrupts osteonal organization and mechanical competence during postnatal cortical bone maturation in rabbits with local metabolic and transcriptional remodeling.
- 1Department of Orthopedics, Chinese PLA General Hospital, Beijing, China.
- 2Department of Rehabilitation Medicine, Chinese PLA General Hospital, Beijing, China.
- 3Health Sciences Institute, China Medical University, Shenyang, China.
Abstract
Introduction
Bone strength depends not only on bone mass and mineral density but also on cortical tissue organization and material quality. Osteons are key structural units of cortical bone, yet whether gut microbiota disturbance affects cortical bone maturation at the osteon level remains unclear.Methods
We first characterized cortical canal remodeling and osteonal organization in New Zealand rabbits at 1, 2, and 3 months of age. Antibiotic-induced microbiota disturbance (AIMD) was then applied during this early osteon-forming window, followed by assessments of gut microbiota composition, osteon morphology, cortical bone micro-CT parameters, mechanical performance, femoral metabolomics, and cortical bone transcriptomics.Results
AIMD reduced gut microbial diversity and altered microbial community structure. At 3 months of age, AIMD-treated rabbits showed impaired osteonal organization, including a reduced proportion of secondary osteons and altered osteon morphology. These osteon-level changes were accompanied by decreased maximum load and stiffness, whereas conventional micro-CT parameters of cortical geometry and mineral density remained unchanged. Multi-omics analyses further revealed local metabolic and transcriptional remodeling involving lipid-related metabolites, bone matrix regulation, osteocyte communication, and metabolic enzyme programs.Discussion
These findings suggest that early gut microbiota disturbance impairs osteon-level cortical bone maturation and reduces mechanical competence. Osteonal organization may therefore represent a sensitive layer of cortical bone quality affected by gut microbiota disturbance during postnatal skeletal development.
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BibTeX
@article{yang2026microbiota,
title = {{Gut microbiota disturbance disrupts osteonal organization and mechanical competence during postnatal cortical bone maturation in rabbits with local metabolic and transcriptional remodeling.}},
author = {Xiaopei Yang and Ziming Geng and Hongji Wang and Gongzi Zhang and Shicheng Luo and Binbin Liu and Yansen Wang and Shuwei Zhang and Lihai Zhang},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1937899},
url = {https://europepmc.org/article/MED/42898502},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut microbiota disturbance disrupts osteonal organization and mechanical competence during postnatal cortical bone maturation in rabbits with local metabolic and transcriptional remodeling.
AU - Xiaopei Yang
AU - Ziming Geng
AU - Hongji Wang
AU - Gongzi Zhang
AU - Shicheng Luo
AU - Binbin Liu
AU - Yansen Wang
AU - Shuwei Zhang
AU - Lihai Zhang
PY - 2026
DA - 2026/10/05
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1937899
UR - https://europepmc.org/article/MED/42898502
AB - Introduction Bone strength depends not only on bone mass and mineral density but also on cortical tissue organization and material quality. Osteons are key structural units of cortical bone, yet whether gut microbiota disturbance affects cortical bone maturation at the osteon level remains unclear.Methods We first characterized cortical canal remodeling and osteonal organization in New Zealand rabbits at 1, 2, and 3 months of age. Antibiotic-induced microbiota disturbance (AIMD) was then applied during this early osteon-forming window, followed by assessments of gut microbiota composition, osteon morphology, cortical bone micro-CT parameters, mechanical performance, femoral metabolomics, and cortical bone transcriptomics.Results AIMD reduced gut microbial diversity and altered microbial community structure. At 3 months of age, AIMD-treated rabbits showed impaired osteonal organization, including a reduced proportion of secondary osteons and altered osteon morphology. These osteon-level changes were accompanied by decreased maximum load and stiffness, whereas conventional micro-CT parameters of cortical geometry and mineral density remained unchanged. Multi-omics analyses further revealed local metabolic and transcriptional remodeling involving lipid-related metabolites, bone matrix regulation, osteocyte communication, and metabolic enzyme programs.Discussion These findings suggest that early gut microbiota disturbance impairs osteon-level cortical bone maturation and reduces mechanical competence. Osteonal organization may therefore represent a sensitive layer of cortical bone quality affected by gut microbiota disturbance during postnatal skeletal development.
SN - 2296-634X
ER -