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通过穿透黏液的聚乙二醇化细菌增强肠道黏膜屏障。

Reinforcement of the intestinal mucosal barrier via mucus-penetrating PEGylated bacteria.

机构信息

Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Nat Biomed Eng. 2024 Jul;8(7):823-841. doi: 10.1038/s41551-024-01224-4. Epub 2024 Jun 5.

Abstract

The breakdown of the gut's mucosal barrier that prevents the infiltration of microorganisms, inflammatory cytokines and toxins into bodily tissues can lead to inflammatory bowel disease and to metabolic and autoimmune diseases. Here we show that the intestinal mucosal barrier can be reinforced via the oral administration of commensal bacteria coated with poly(ethylene glycol) (PEG) to facilitate their penetration into mucus. In mice with intestinal homoeostatic imbalance, mucus-penetrating PEGylated bacteria preferentially localized in mucus at the lower gastrointestinal tract, inhibited the invasion of pathogenic bacteria, maintained homoeostasis of the gut microbiota, stimulated the secretion of mucus and the expression of tight junctions, and prevented the mice from developing colitis and diabetes. Orally delivered PEGylated bacteria may help prevent and treat gastrointestinal disorders.

摘要

肠道黏膜屏障的破坏会导致微生物、炎症细胞因子和毒素渗透到身体组织中,从而引发炎症性肠病和代谢及自身免疫性疾病。在这里,我们表明可以通过口服用聚乙二醇(PEG)包裹的共生菌来增强肠道黏膜屏障,以促进其穿透黏液。在肠道内稳态失衡的小鼠中,穿透黏液的 PEG 化细菌优先定位于下消化道的黏液中,抑制了致病菌的入侵,维持了肠道微生物组的内稳态,刺激了黏液的分泌和紧密连接的表达,防止了小鼠发生结肠炎和糖尿病。口服递送的 PEG 化细菌可能有助于预防和治疗胃肠道疾病。

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