Alty Jill W, Barnes Carolyn E, Nicoli Agnese M, Turner Bradley S, Beneman Ekua A, Dugan Amanda E, Brucks Spencer D, Kruger Austin G, Schrock Richard R, Ribbeck Katharina, Kiessling Laura L
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
ACS Cent Sci. 2025 Jun 2;11(6):918-926. doi: 10.1021/acscentsci.5c00317. eCollection 2025 Jun 25.
The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed -glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.
人类微生物群中细菌细胞的数量至少与人类细胞一样多。一些细菌具有益处，比如改善肠道屏障功能、抑制致病共生菌生长以及调节免疫力。这些益处使得益生菌广受欢迎，但益生菌在衬于所有上皮细胞的黏膜层中的定殖效率往往较低，从而阻碍了其留存。黏蛋白是黏液的主要成分，对于微生物群落的组织和调节至关重要。黏蛋白与益生菌相互作用的分子机制仍未得到充分研究，部分原因是无法精准操控天然黏蛋白序列或其聚糖。在此，我们使用具有明确聚糖呈现方式的合成黏蛋白，来探究黏液与三种益生菌乳酸杆菌之间的聚糖依赖性相互作用。培养细菌的营养条件会影响聚糖结合偏好，这表明黏蛋白与益生菌的相互作用会随营养可利用性而改变。向天然黏蛋白中添加合成黏蛋白可增加黏附。此外，糖苷酶活性的增加表明天然和合成黏蛋白都具有益生元的功能，因为益生菌能够裂解所展示的聚糖。因此，合成黏蛋白可培养目标益生菌并增加作为结合位点的黏附，凸显了它们作为阐明天然黏蛋白功能的工具以及作为促进人类健康的有前景制剂的价值。
