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聚-β-羟基丁酸酯通过约翰逊乳杆菌生物膜介导的磺粘蛋白成熟缓解腹泻和结肠炎。

Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.

出版信息

Sci China Life Sci. 2023 Jul;66(7):1569-1588. doi: 10.1007/s11427-022-2213-6. Epub 2022 Dec 23.

Abstract

Maintainance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease (IBD). However, the mechanisms underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Herein, we biosynthesized poly-β-hydroxybutyrate (PHB) and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transplantation and clearance together demonstrate that PHB promoting sulfomucin is mediated by Lactobacillus johnsonii (L. johnsonii). Further studies revealed that PHB provides a favorable niche for L. johnsonii biofilm formation to resist disturbance and support its growth. L. johnsonii-biofilm alleviates colitis by regulating fucose residues to promote goblet cell differentiation and subsequent sulfomucin maturation. Importantly, PHB alleviates colitis by enhancing sulfomucin secretion and maturation in a L. johnsonii-dependent manner. PHB represents a class of guardians, acting as a safe probiotic-biofilm delivery system that significantly promotes probiotic proliferation. Altogether, this study adds weight to the possible role of probiotics and functional materials in the treatment of intestinal inflammation. The application of PHB and biofilm self-coating L. johnsonii carries high translational potential and may be of clinical relevance.

摘要

维持磺基粘蛋白的水平是治疗腹泻和炎症性肠病(IBD)的关键终点。然而,微生物感知磺基粘蛋白的机制还知之甚少,迄今为止,还没有针对 IBD 中磺基粘蛋白分泌和成熟的治疗方法。在此,我们生物合成了聚-β-羟基丁酸(PHB),并发现 PHB 可以通过增强磺基粘蛋白的分化来缓解腹泻和结肠炎引起的炎症。微生物群移植和清除共同表明,PHB 促进磺基粘蛋白的作用是由约翰逊乳杆菌(L. johnsonii)介导的。进一步的研究表明,PHB 为 L. johnsonii 生物膜的形成提供了一个有利的小生境,以抵抗干扰并支持其生长。L. johnsonii 生物膜通过调节岩藻糖残基来缓解结肠炎,从而促进杯状细胞分化和随后的磺基粘蛋白成熟。重要的是,PHB 通过增强 L. johnsonii 依赖性的磺基粘蛋白分泌和成熟来缓解结肠炎。PHB 代表了一类守护者,作为一种安全的益生菌-生物膜输送系统,显著促进了益生菌的增殖。总的来说,这项研究为益生菌和功能材料在治疗肠道炎症中的可能作用提供了更多依据。PHB 的应用和生物膜自涂覆的 L. johnsonii 具有很高的转化潜力,可能具有临床相关性。

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