Engineered synbiotic microspheres enable system-level reprogramming of the gut-immune-vascular axis in chronic inflammatory vascular disease.

Authors

Lin Shen, Mengqian Zhai, Zhangyu Yang, Junchao Yu, Ziyu Pang, Zijian Fang, Xingru Ding, Jiahui Xu, Yingtao Hu, Shiji Fang, Gaofeng Shu, Yang Yang, Lingchun Lv, Susu Zhang, Jian Xu, Jianhua Wu, Weiqian Chen, Chenying Lu, Minjiang Chen, Jiansong Ji

Published in

Science advances. Volume 12. Issue 45. Pages eaeg1718. Nov 06, 2026. Epub Nov 04, 2026.

Abstract

Chronic inflammatory vascular diseases are increasingly recognized as systemic disorders sustained by maladaptive cross-organ immunometabolic coupling, yet current therapeutic strategies remain largely lesion-centered and fail to address upstream drivers of disease persistence. Here, we identify the gut-immune-vascular axis as a system-level pathogenic unit that integrates gut microbial dysbiosis, intestinal barrier dysfunction, metabolic imbalance, and vascular immune activation into a self-reinforcing pathological circuit. Through integrated clinical profiling and cross-species validation, we demonstrate that disruption of this axis is characterized by coordinated probiotic depletion, expansion of proinflammatory taxa, translocation of microbial endotoxins, accumulation of microbiota-derived metabolites, and macrophage polarization toward a proinflammatory phenotype along the gut-vascular continuum. To therapeutically target this axis, we engineer enzyme-responsive synbiotic microspheres that codeliver probiotics, a microbial metabolic pathway inhibitor, and a prebiotic within a protective polymeric matrix, enabling site-specific intestinal activation and coordinated microbiota-metabolic modulation. This engineered system restores intestinal barrier integrity, reprograms microbial ecology and metabolite output, suppresses immunometabolic dysfunction, and robustly attenuates pathological vascular remodeling across cellular, murine, and large-animal models, with in-stent restenosis serving as a representative disease context. Collectively, this work establishes axis-oriented immunometabolic reprogramming as a generalizable therapeutic paradigm and highlights engineered synbiotic platforms as scalable tools for system-level intervention in chronic inflammatory diseases.

PMID:
42981406
Bibliographic data and abstract were imported from PubMed on 05 Nov 2026.

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