陕西师范大学杨兴斌等研究人员合作发现，不可消化的水苏糖结合小肠上皮膜上HSP90β调节外泌体miRNA。该研究于2024年11月18日在线发表于国际一流学术期刊《细胞—代谢》。

寡糖通常被认为是小肠中的“过客”。然而，研究人员重新定义了这一认识，揭示了寡糖水苏糖（stachyose）的新功能。它能够结合小肠上皮细胞膜上的HSP90β的疏水性残基，从而重新编程外泌体miRNA的表达谱。

通过CRISPR-Cas9介导的HSP90β敲除实验，研究人员消除了水苏糖在细胞膜上的积累及其对这些miRNA的调控作用。值得注意的是，水苏糖对这些miRNA的调控与其作为益生元的作用无关，这一点通过在伪无菌小鼠中观察到水苏糖改变的粪便miRNA得到了证实。

这些水苏糖改变的miRNA进一步塑造了结肠微生物群，尤其是小鼠体内的乳酸菌群。在这些miRNA中，miR-30a-5p在水苏糖处理后在小鼠和人类粪便中都下调（Log₂FC < −2），并能特异性抑制乳酸菌（Lactobacillus reuteri）的生长。

这些发现构建了一个新的调控轴：水苏糖-肠道miRNA-肠道微生物群，并揭示了一个前所未有的机制，即寡糖通过膜蛋白HSP90β直接与肠上皮细胞进行“对话”。

附：英文原文

Title: Nondigestible stachyose binds membranous HSP90β on small intestinal epithelium to regulate the exosomal miRNAs: A new function and mechanism

Author: Ting Li, Yueyue Liu, Tianchi Duan, Chao Guo, Bin Liu, Xiuqiong Fu, Lu Wang, Xiaoyuan Wang, Xinyue Dong, Chennan Wang, Yalong Lu, Yu Wang, Lin Shi, Honglei Tian, Xingbin Yang

Issue&Volume: 2024-11-18

Abstract: Oligosaccharides are conventionally recognized as “passersby” in the small intestine. However, our research has reframed this understanding by uncovering a new function of oligosaccharide stachyose, which binds hydrophobic residues of membranous HSP90β on small intestinal epithelial cells, thus reprograming the exosomal miRNA profile. CRISPR-Cas9-mediated HSP90β knockout abolished the accumulation of stachyose on cell membrane and its regulatory effects on these miRNAs. Notably, stachyose’s regulation on these miRNAs is independent of its prebiotic role, as evidenced by the observation of stachyose-altered fecal miRNAs in pseudo-germ-free mice. These stachyose-altered miRNAs further shaped colonic microbiome, especially harboring Lactobacillus in mice. Thereinto, miR-30a-5p that was downregulated (Log2FC < 2) in both mice and human feces following stachyose treatment could specifically suppress the growth of Lactobacillus reuteri. These findings build a new regulatory axis of stachyose-intestinal miRNAs-gut microbiota and unveil a previously unknown mechanism underlying the direct “talk” of oligosaccharides to intestine epithelium via membranous HSP90β.

DOI: 10.1016/j.cmet.2024.10.012

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00408-X