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Peer-reviewedCC BYJournal of Extracellular Vesicles

Extracellular Vesicle‐Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism

  1. 1Institute of Subtropical Agriculture the Chinese Academy of Sciences Changsha China
  2. 2College of Standardisation China Jiliang University Hangzhou China

Abstract

The gut microbiota plays a critical role in regulating intestinal lipid metabolism, yet the mechanisms governing microbiota–host interactions during lipid uptake remain unclear. Here, we examined the relationship between fat digestibility and gut microbial composition, and found that piglets with higher apparent crude fat digestibility exhibited enhanced lipid absorption and oxidation, accompanied by reduced abundance of Clostridium butyricum in the ileal mucosa. Furthermore, oral administration of C. butyricum suppressed intestinal lipid absorption and oxidation by inhibiting PPARα signaling. Mechanistically, extracellular vesicles (EVs) derived from C. butyricum can enter intestinal epithelial cells and mediate the anti‐lipid absorption effects by delivering miRNA‐like RNAs (milRNAs), particularly milRNA‐3020179, which primarily targeted host genes including PPARα and Rxra. Supplementation with C. butyricum or its EVs prevented lipid accumulation and attenuated the development of metabolic abnormalities in high‐fat diet‐fed mice, whereas deletion of milRNA‐3020179 in C. butyricum abolished its effects on lipid deposition in intestinal organoids. Collectively, these findings identify C. butyricum‐derived EV milRNAs as candidate microbial regulators of host lipid metabolism through modulation of PPARα signaling, providing insights into microbiota‐driven control of intestinal lipid homeostasis.

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BibTeX
@article{hu2026extracellular,
  title = {{Extracellular Vesicle‐Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism}},
  author = {Hong Hu and Yiwen He and Jing Liang and Qi Han and Xuqing Liang and Guangtian Cao and Yulong Tang and Liuqin He and Yulong Yin and Xihong Zhou},
  journal = {Journal of Extracellular Vesicles},
  year = {2026},
  month = oct,
  doi = {10.1002/jev2.70381},
  url = {https://doi.org/10.1002/jev2.70381},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Extracellular Vesicle‐Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism
AU  - Hong Hu
AU  - Yiwen He
AU  - Jing Liang
AU  - Qi Han
AU  - Xuqing Liang
AU  - Guangtian Cao
AU  - Yulong Tang
AU  - Liuqin He
AU  - Yulong Yin
AU  - Xihong Zhou
PY  - 2026
DA  - 2026/10/26
JO  - Journal of Extracellular Vesicles
DO  - 10.1002/jev2.70381
UR  - https://doi.org/10.1002/jev2.70381
AB  - The gut microbiota plays a critical role in regulating intestinal lipid metabolism, yet the mechanisms governing microbiota–host interactions during lipid uptake remain unclear. Here, we examined the relationship between fat digestibility and gut microbial composition, and found that piglets with higher apparent crude fat digestibility exhibited enhanced lipid absorption and oxidation, accompanied by reduced abundance of Clostridium butyricum in the ileal mucosa. Furthermore, oral administration of C. butyricum suppressed intestinal lipid absorption and oxidation by inhibiting PPARα signaling. Mechanistically, extracellular vesicles (EVs) derived from C. butyricum can enter intestinal epithelial cells and mediate the anti‐lipid absorption effects by delivering miRNA‐like RNAs (milRNAs), particularly milRNA‐3020179, which primarily targeted host genes including PPARα and Rxra. Supplementation with C. butyricum or its EVs prevented lipid accumulation and attenuated the development of metabolic abnormalities in high‐fat diet‐fed mice, whereas deletion of milRNA‐3020179 in C. butyricum abolished its effects on lipid deposition in intestinal organoids. Collectively, these findings identify C. butyricum‐derived EV milRNAs as candidate microbial regulators of host lipid metabolism through modulation of PPARα signaling, providing insights into microbiota‐driven control of intestinal lipid homeostasis.
SN  - 2001-3078
ER  -