Dynamic feedback BacGuard anchors microbial metabolism to host symbiosis in real-time ulcerative colitis therapy

  • Bioact Mater. 2026 Jun 6:65:365-379. doi: 10.1016/j.bioactmat.2026.05.060.
Zeyuan Jin  1 ,  Yaqi Zhang  2 ,  Zilong Zhong  1 ,  Zipeng Shen  3 ,  Lei Huang  1 ,  Haijun Hu  1 ,  Xiping Chen  1 ,  Wenxing Liu  1  3 ,  Lanjuan Li  2  4 ,  Changyou Gao  1  3  5  6
Affiliations
  • 1. Zhejiang Key Laboratory of Advanced Organic Materials and Technologies, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
  • 2. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • 3. Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China.
  • 4. Yuhang Institute of Medical Science Innovation and Transformation, Hangzhou, 311100, China.
  • 5. The State Key Laboratory of Transvascular Implantation Devices, Zhejiang University, Hangzhou, 310009, China.
  • 6. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China.
PMID: 42290978 DOI: 10.1016/j.bioactmat.2026.05.060
Abstract

The escalating global burden of ulcerative colitis (UC) underscores the limitations of conventional anti-inflammatory therapies. Although multi-omics insights have propelled gut microbiota modulation to the forefront of therapeutic innovation, current strategies relying on probiotics or fecal transplants remain constrained by empirical designs due to the lack of spatiotemporal precision and real-time monitoring of microbial metabolic vitality in situ. In this study, BacGuard, a metabolically orthogonal microgel platform, was developed to unify the probiotic surveillance and guided dynamic dose regulation with spatially targeted microbiota-associated metabolic modulation. Our core design featured a β-xylosidase-activated chemiluminescent probe (XOS-CL) that was conjugated with xylooligosaccharide-based hyperbranched Polymers (HBXOK) and orally delivered via microgels. Thereby, this system enabled real-time monitoring of probiotic abundance and metabolic activity in the colon through enzyme-responsive signaling, while simultaneously promoting short-chain fatty acid (SCFA) production via redirected Bacterial metabolic flux. This dual-action system created a self-reinforcing therapeutic loop and optically quantifying the microbial activity in a dynamic manner. By resolving the causal disconnects between enzymatic activity, microbiota proliferation, and host interactions, the BacGuard bridged the diagnostic metrics to functional therapeutic outcomes. Anchoring both sensing and treatment to microbial metabolic flux, our platform reimagined the precision gut ecosystem engineering, establishing an image-guided dynamic dose regulation framework that actively preserved the microbiota-host symbiosis through in-time and function-adaptive modulation.

Keywords
Chemiluminescence; Gut microbiota; Microgels; Ulcerative colitis; β-Xylosidase monitoring.
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