斯坦福大学Kerwyn Casey Huang小组近日取得一项新成果。经过不懈努力，他们报道了婴儿肠道共生体短双歧杆菌的基因组规模资源揭示了定植和宿主-微生物相互作用的遗传决定因素。相关论文于2025年3月10日发表在《细胞》杂志上。
为了解决这些主要的知识空白，该团队以大规模的遗传方法为主题，在短双歧杆菌中创建突变适应度纲要。首先，课题组生成了一个高密度随机条形码转座子插入池，并对其进行了主题化，以确定无菌小鼠和鸡在多种饮食和数百种体外扰动下定植期间的适应性需求。其次，为了进行机制研究，研究小组构建了一个包含1,462个基因的插入菌株的有序集合。该课题组人员利用这些工具揭示了群落和饮食对定植的特定要求，并将免疫调节分子的产生与生长益处联系起来。这些研究成果将促进对这一重要有益微生物的进一步研究。
据了解，双歧杆菌是婴儿期人类肠道微生物群的主要组成部分，影响营养、免疫发育和对感染的抵抗力。尽管人们对双歧杆菌作为一种活的生物疗法很感兴趣，但他们对双歧杆菌的定植、宿主-微生物相互作用和促进健康作用的理解是有限的。
附：英文原文
Title: Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions
Author: Anthony L. Shiver, Jiawei Sun, Rebecca Culver, Arvie Violette, Char Wynter, Marta Nieckarz, Samara Paula Mattiello, Prabhjot Kaur Sekhon, Francesca Bottacini, Lisa Friess, Hans K. Carlson, Daniel P.G.H. Wong, Steven Higginbottom, Meredith Weglarz, Weigao Wang, Benjamin D. Knapp, Emma Guiberson, Juan Sanchez, Po-Hsun Huang, Paulo A. Garcia, Cullen R. Buie, Benjamin H. Good, Brian DeFelice, Felipe Cava, Joy Scaria, Justin L. Sonnenburg, Douwe Van Sinderen, Adam M. Deutschbauer, Kerwyn Casey Huang
Issue&Volume: 2025-03-10
Abstract: Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.
DOI: 10.1016/j.cell.2025.02.010
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00195-3