Portulaca oleracea L.-derived exosome-like nanoparticles ameliorate colitis by modulating gut microbiota and metabolites to reduce endoplasmic reticulum stress

doi:10.3748/wjg.120885

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Oct 7, 2026; 32(37): 120885
Published online Oct 7, 2026. doi: 10.3748/wjg.120885

Portulaca oleracea L.-derived exosome-like nanoparticles ameliorate colitis by modulating gut microbiota and metabolites to reduce endoplasmic reticulum stress

Xiao-Yan Liu, Zi-Xuan Liu, Wei-Wei Tan, Wei-Bing Zhang, Dan Qiao, Shuo-Han Chen, Ya-Li Zhang, Lie Zheng, Wen-Song Ge, Yan-Cheng Dai

Xiao-Yan Liu, Zi-Xuan Liu, Wei-Wei Tan, Wei-Bing Zhang, Dan Qiao, Shuo-Han Chen, Yan-Cheng Dai, Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China

Ya-Li Zhang, Institute of Digestive Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Lie Zheng, Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China

Wen-Song Ge, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China

Co-first authors: Xiao-Yan Liu and Zi-Xuan Liu.

Co-corresponding authors: Wen-Song Ge and Yan-Cheng Dai.

Author contributions: Liu XY and Liu ZX performed most of the experiments and contributed equally to this study as co-first authors. Dai YC designed the study, analyzed the data, and wrote the manuscript. Ge WS contributed to study design and reviewed the manuscript. Zhang YL and Zheng L prepared and characterized exosome-like nanoparticles. Tan WW, Zhang WB, Qiao D and Chen SH contributed to performed the experiments and analyzed data. All authors approved the final manuscript. Both Dai YC and Ge WS have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors.

AI contribution statement: AI tools (specifically DeepSeek) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.

Supported by the National Natural Science Foundation of China, No. 81873253 and No. 82574996; the Shanghai Natural Science Foundation, No. 22ZR1458800; the Scientific Research Project Plan of Shanghai Municipal Health Commission, No. 202240385; Hongkou District Health Committee, No. HKZK2020A01; Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project, No. TZKN-CXRC-16; Project of Shaanxi Administration of Traditional Chinese Medicine, No. SZY-KJCYC-2025-JC-010; and Shaanxi Province Key Research and Development Plan Project-Social Development Field, No. 2025SF-YBXM-498.

Institutional animal care and use committee statement: According to the National Guidelines for Experimental Animal Welfare, all animal experiment protocols were approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (Approval No. PZSHUTCM2302270016).

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: Data are available via MetaboLights with identifier MTBLS14499. 16S sequencing data (NCBI SRA): PRJNA1466611. The other data that support the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Yan-Cheng Dai, PhD, Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital Shanghai University of Traditional Chinese Medicine, No. 230 Baoding Road, Hongkou District, Shanghai 200082, China. daiyancheng2005@126.com

Received: March 11, 2026
Revised: May 3, 2026
Accepted: June 23, 2026
Published online: October 7, 2026
Processing time: 174 Days and 23.5 Hours

Abstract

BACKGROUND

Ulcerative colitis (UC) is associated with excessive endoplasmic reticulum stress (ERS) and gut microbiota dysbiosis. Portulaca oleracea L. (P. oleracea L.), as a food-as-medicine, has demonstrated potential in alleviating colitis symptoms, enhancing barrier function, anti-inflammatory, antioxidant, and cleaning up free radical. However, its role in modulating ERS, gut microbiota and metabolites remained unclear.

AIM

To explore how P. oleracea L.-derived exosome-like nanoparticles (PELNs) alleviate colitis in mice by modulating gut microbiota and metabolites to mitigate ERS.

METHODS

In this study, PELNs were isolated and characterized. Colitis was induced by dextran sulfate sodium and microbiota-transplanted mouse models, followed by relevant drug intervention period. Mechanistic investigations were to examine inflammatory factors, oxidative stress and ERS. Fecal samples collection for gut microbiota and metabolite was analyzed.

RESULTS

This study demonstrated that PELNs intervention alleviated colitis through the modulation of the intestinal microbial community and its associated metabolites, thereby reducing ERS by inhibiting the PERK-eIF2α-ATF4 signaling pathway, reducing inflammatory cytokines, and restoring tight junctions in intestinal epithelial cells.

CONCLUSION

PELNs ameliorate UC by modulating gut microbiota and metabolites, reducing ERS. These findings highlight PELNs as a novel, food-derived, colon-targeted therapeutic, offering a promising approach for UC treatment.

Keywords: Portulaca oleracea L.-derived exosome-like nanoparticles; Ulcerative colitis; Endoplasmic reticulum stress; Tight junction; PERK-eIF2α-ATF4 signaling pathway; Gut microbiota; Metabolites

Core Tip: The role of Portulaca oleracea L. (P. oleracea L.) in modulating endoplasmic reticulum stress, gut microbiota and metabolites remained unclear. To investigate this, we prepared exosome-like nanoparticles derived from P. oleracea L. and modeled colitis induced by dextran sulfate sodium and microbiota-transplanted mouse. We found that P. oleracea L.-derived exosome-like nanoparticles (PELNs) intervention alleviated colitis through the modulation of the intestinal microbial community and metabolites. PELNs as a novel, food-derived, colon-targeted therapeutic, offering a promising approach for ulcerative colitis treatment.