Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo.
Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo.
复制标题
DOI：
10.7554/elife.64478
复制
发表时间：
2021-03-08
期刊：
影响因子：
7.7
通讯作者：
Gordon JI
中科院分区：
文献类型：
--
作者：
Wesener DA;Beller ZW;Peters SL;Rajabi A;Dimartino G;Giannone RJ;Hettich RL;Gordon JI
需要测量体内肠道微生物群生化活性的方法来表征其在健康和疾病中的功能状态。为了说明一种方法，从豌豆纤维中分离出一种含阿拉伯聚糖的多糖，确定其结构，并使用正向遗传和蛋白质组学分析来比较其与未分级豌豆纤维和甜菜阿拉伯聚糖对gnotobiotic小鼠中人类肠道细菌菌株聚生体的影响。我们生产了“微生物群功能活性生物传感器”（MFB），由共价连接到荧光顺磁性显微镜玻璃珠表面的聚糖组成。将三种MFB（各自含有独特的聚糖/荧光团组合）同时经口灌胃到无菌小鼠中，从其肠道中回收，并进行分析以直接定量不同人类饮食环境中结构不同的阿拉伯聚糖的细菌代谢。豌豆纤维阿拉伯聚糖和另一种多糖（葡甘露聚糖）在珠表面上的共定位增强葡甘露聚糖的体内降解。MFB代表了开发新的益生元和更有营养的食品的潜在多功能平台。生活在肠道中的数万亿微生物帮助人类和其他动物消化食物。在这个过程中，微生物为自己和动物提供必要的营养。更多地了解食物成分和肠道细菌的相互作用可以帮助科学家更好地了解不同的饮食如何影响人类健康。目前，研究这些复杂的相互作用具有挑战性，但测量肠道中微生物营养加工的新技术可能会有所帮助。现在，Wesener等人表明，可吞咽的显微生物传感器可以测量肠道细菌如何分解食物中的营养物质。为了制造生物传感器，Wesener等人将从豌豆中提取的复合碳水化合物和荧光标记物连接到显微镜下的珠子上。在实验中，将人类肠道微生物定植的小鼠与传统的低纤维西方饮食一起喂食珠子沿着。一些动物还接受了纤维补充剂。然后在消化后从肠中回收微观珠粒，并测量珠粒上剩余的碳水化合物。还检查了肠道微生物组的遗传组成和微生物基因的表达。实验揭示了肠道微生物消耗的豌豆碳水化合物，并表明在微珠表面将某些碳水化合物配对在一起可以增加接受纤维补充剂的小鼠的消化。如果未来的研究证明Wesener等人创造的微珠生物传感器对人类摄取是安全的，它们可以用来帮助诊断一个人的肠道微生物群处理不同食物的能力。使用微珠传感器的研究还可以帮助科学家开发更有营养的食物或补充剂，促进对健康重要的微生物的生长。
Methods for measuring gut microbiota biochemical activities in vivo are needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was isolated from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced ‘Microbiota Functional Activity Biosensors’ (MFABs) consisting of glycans covalently linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhanced in vivo degradation of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods. Tens of trillions of microbes living in the gut help humans and other animals digest their food. In the process, the microbes provide necessary nutrients for themselves and the animal. Learning more about the interaction of food components and gut bacteria could help scientists to better understand how different diets affect human health. Currently, studying these complex interactions is challenging, but new technologies that measure microbial nutrient processing in the gut could help. Now, Wesener et al. show that swallowable microscopic biosensors can measure how gut bacteria break down nutrients from food. To make the biosensors, Wesener et al. attached complex carbohydrates extracted from peas and fluorescent tags to microscopic beads. In the experiments, mice colonized with human gut microbes were fed the beads along with a traditional low fiber, Western diet. Some of the animals also received fiber supplements. The microscopic beads were then recovered from the intestines after digestion and the remaining carbohydrates on the beads were measured. The genetic makeup of the gut microbiome and the expression of microbial genes was also examined. The experiments revealed which pea carbohydrates the gut microbes consumed and showed that pairing certain carbohydrates together on the microbead surface increased their digestion in mice that received fiber supplements. If future studies prove that the microbead biosensors created by Wesener et al. are safe for humans to ingest, they could be used to help diagnose how well a person’s gut microbiota can process different foods. Studies using the microbead sensors may also help scientists develop more nutritious foods or supplements that promote the growth of microbes important for health.