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Peer-reviewedCC BYTheranostics

Oral inulin prebiotic encapsulating Cortex Fraxini extracellular vesicles alleviates colitis and associated renal stress via reinforcing intestinal barriers and remodeling microbiota.

  • Meihong Chai1
  • Junlong Fu2
  • Mengjie Zhang3
  • Xing Pei4
  • Xingzhou Liu2
  • Bing Xiao1
  • Bowen Gao2
  • Jingya Wei2
  • Baosen Yue1
  • Mingxin Zhang5
  • Mingzhen Zhang5
  • Juan Jin6
6 affiliations
  1. 1Department of Pharmacy, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, 710021, China.
  2. 2Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
  3. 3School of Life Science; School of Interdisciplinary Science; Aerospace Center Hospital; Key Laboratory of Molecular Medicine and Biotherapy; Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering; Beijing Institute of Technology, Beijing, 100081, China.
  4. 4Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
  5. 5Department of Gastroenterology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China.
  6. 6Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, China.
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Abstract

Background: Gut-kidney axis dysfunction contributes to extraintestinal complications in inflammatory bowel disease (IBD), yet effective therapeutic strategies targeting this axis remain limited. This study developed an oral prebiotic delivery system by encapsulating Cortex Fraxini-derived extracellular vesicles (CF-EVs) within an inulin-based hydrogel (CF-EVs@Inulin) and evaluated its therapeutic potential in ulcerative colitis and associated renal injury. Methods: CF-EVs were isolated and characterized for morphology and antioxidant activity. An inulin-based hydrogel was employed to encapsulate CF-EVs and improve gastrointestinal stability and colonic retention. Therapeutic efficacy was assessed in dextran sulfate sodium (DSS)-induced acute colitis mice, including antibiotic-pretreated groups. Gut microbiota composition, intestinal barrier integrity, intestinal permeability, lipopolysaccharide (LPS) translocation, renal TLR4/NF-κB signaling, and renal injury markers were analyzed. Results: CF-EVs exhibited typical vesicular morphology and potent ROS-scavenging activity. CF-EVs@Inulin showed enhanced gastrointestinal stability and prolonged retention in the colon. Treatment with CF-EVs@Inulin significantly ameliorated colitis symptoms, restored mucus and tight junction barriers, and remodeled gut microbiota composition. These protective effects were largely attenuated following microbiota depletion. Mechanistically, CF-EVs@Inulin reduced intestinal permeability and circulating LPS levels, suppressed renal TLR4/NF-κB activation, improved renal function, and decreased the expression of kidney injury markers KIM-1 and NGAL. Conclusion: CF-EVs@Inulin alleviates colitis-associated early renal stress by restoring intestinal barrier integrity and gut microbiota homeostasis, thereby interrupting the LPS-TLR4/NF-κB signaling pathway. These findings highlight the therapeutic potential of prebiotic-encapsulated CF-EVs as a promising strategy for ulcerative colitis and gut-kidney axis-related complications.

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Cite

BibTeXRIS
BibTeX
@article{chai2026oral,
  title = {{Oral inulin prebiotic encapsulating Cortex Fraxini extracellular vesicles alleviates colitis and associated renal stress via reinforcing intestinal barriers and remodeling microbiota.}},
  author = {Meihong Chai and Junlong Fu and Mengjie Zhang and Xing Pei and Xingzhou Liu and Bing Xiao and Bowen Gao and Jingya Wei and Baosen Yue and Mingxin Zhang and Mingzhen Zhang and Juan Jin},
  journal = {Theranostics},
  year = {2026},
  month = sep,
  doi = {10.7150/thno.139484},
  url = {https://europepmc.org/article/MED/42909239},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Oral inulin prebiotic encapsulating Cortex Fraxini extracellular vesicles alleviates colitis and associated renal stress via reinforcing intestinal barriers and remodeling microbiota.
AU  - Meihong Chai
AU  - Junlong Fu
AU  - Mengjie Zhang
AU  - Xing Pei
AU  - Xingzhou Liu
AU  - Bing Xiao
AU  - Bowen Gao
AU  - Jingya Wei
AU  - Baosen Yue
AU  - Mingxin Zhang
AU  - Mingzhen Zhang
AU  - Juan Jin
PY  - 2026
DA  - 2026/09/02
JO  - Theranostics
DO  - 10.7150/thno.139484
UR  - https://europepmc.org/article/MED/42909239
AB  - Background: Gut-kidney axis dysfunction contributes to extraintestinal complications in inflammatory bowel disease (IBD), yet effective therapeutic strategies targeting this axis remain limited. This study developed an oral prebiotic delivery system by encapsulating Cortex Fraxini-derived extracellular vesicles (CF-EVs) within an inulin-based hydrogel (CF-EVs@Inulin) and evaluated its therapeutic potential in ulcerative colitis and associated renal injury. Methods: CF-EVs were isolated and characterized for morphology and antioxidant activity. An inulin-based hydrogel was employed to encapsulate CF-EVs and improve gastrointestinal stability and colonic retention. Therapeutic efficacy was assessed in dextran sulfate sodium (DSS)-induced acute colitis mice, including antibiotic-pretreated groups. Gut microbiota composition, intestinal barrier integrity, intestinal permeability, lipopolysaccharide (LPS) translocation, renal TLR4/NF-κB signaling, and renal injury markers were analyzed. Results: CF-EVs exhibited typical vesicular morphology and potent ROS-scavenging activity. CF-EVs@Inulin showed enhanced gastrointestinal stability and prolonged retention in the colon. Treatment with CF-EVs@Inulin significantly ameliorated colitis symptoms, restored mucus and tight junction barriers, and remodeled gut microbiota composition. These protective effects were largely attenuated following microbiota depletion. Mechanistically, CF-EVs@Inulin reduced intestinal permeability and circulating LPS levels, suppressed renal TLR4/NF-κB activation, improved renal function, and decreased the expression of kidney injury markers KIM-1 and NGAL. Conclusion: CF-EVs@Inulin alleviates colitis-associated early renal stress by restoring intestinal barrier integrity and gut microbiota homeostasis, thereby interrupting the LPS-TLR4/NF-κB signaling pathway. These findings highlight the therapeutic potential of prebiotic-encapsulated CF-EVs as a promising strategy for ulcerative colitis and gut-kidney axis-related complications.
SN  - 1838-7640
ER  -