ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Car@PLGA-NPs Target Gut Microbiota-ER Stress Axis to Combat Diabetes
Provisionally accepted
- 1The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
- 2The Second Clinical Medical School of Guizhou University of Traditional Chinese Medicine, Gui, China
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BackgroundIntroduction: Previous studies have demonstrated that carvacrol (Car) ameliorates vascular and hepatic injury in db/db mice, but its low bioavailability limits clinical translation. Methods: To address this, this study constructed carvacrol-loaded polymeric nanoparticles (Car@PLGA-NPs) to enhance carvacrol bioavailabilityutilization and fully explorefurther investigate its novel mechanisms of action on islet function and gut homeostasis in a diabetic model. We used Utilizing C57BL/6J db/db mice, we measured to measure serum fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance (ITT), and lipid profiles. Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota composition and its correlation with host indices. 设置了格式: 非上标/ 下标 设置了格式: 上标 设置了格式: 字体: 非加粗 设置了格式: 字体: 非加粗 This is a provisional file, not the final typeset article Pancreatic and intestinal tissues underwent histopathological staining, immunofluorescence, and Western blotting to detect endoplasmic reticulum (ER) stress-related protein expression levels (p-IRE1α, XBP1S, PERK, p-eIF2αElF2α). Results: Results demonstrated that Car@PLGA-NPs, compared to free carvacrol, significantly improved insulin sensitivity, reduced fasting blood glucose, ameliorated dyslipidemia, attenuated inflammation, and mitigated oxidative stress in db/db mice. 16S rRNA sequencing revealed that Car@PLGA-NPs remodeled the gut microbiota composition, with Alloprevotella abundance showing a negative correlation with colonic ER stress proteins (p-IRE1α and p-eIF2αElF2α). Immunofluorescence and Western blotting further confirmed that Car@PLGA-NPs significantly suppressed the expression of ER stress-related proteins (p-IRE1α, XBP1S, PERK, p-EIF2αElF2α) in both islet and colonic tissues, demonstrating superior efficacy to free carvacrol. ConclusionsDiscussion: Collectively, this study confirms that the PLGA nanocarrier effectively enhances carvacrol bioavailability. Car@PLGA-NPs improve islet function and intestinal homeostasis in diabetic mice by remodeling the gut microbiota and subsequently inhibiting ER stress in pancreatic and intestinal tissues, providing a novel nano-drug delivery system and a "microbiota-ER stress" regulatory axis for diabetes treatment.
Keywords: carvacrol, Endoplasmic Reticulum Stress, Gut Microbiota, islet, nanoparticle
Received: 16 Jul 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Zhao, Chen, Qing, Zhao, Xiong, Tong and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Zhao
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