Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Research Computing, University of North Carolina, Chapel Hill, NC 27599, USA.
Nutrients. 2018 Oct 16;10(10):1517. doi: 10.3390/nu10101517.
Lactose intolerance, characterized by a decrease in host lactase expression, affects approximately 75% of the world population. Galacto-oligosaccharides (GOS) are prebiotics that have been shown to alleviate symptoms of lactose intolerance and to modulate the intestinal microbiota, promoting the growth of beneficial microorganisms. We hypothesized that mechanisms of GOS utilization by intestinal bacteria are variable, impacting efficacy and response, with differences occurring at the strain level. This study aimed to determine the mechanisms by which human-derived strains metabolize GOS. Genomic comparisons between strains revealed differences in carbohydrate utilization components, including transporters, enzymes for degradation, and transcriptional regulation, despite a high overall sequence identity (>95%) between strains. Physiological and transcriptomics analyses showed distinct differences in carbohydrate metabolism profiles and GOS utilization between strains. A putative operon responsible for GOS utilization was identified and characterized by genetic disruption of the 6-phospho-β-galactosidase, which had a critical role in GOS utilization. Our findings highlight the importance of strain-specific bacterial metabolism in the selection of probiotics and synbiotics to alleviate symptoms of gastrointestinal disorders including lactose intolerance.
乳糖不耐受，其特征是宿主乳糖酶表达减少，影响了大约 75%的世界人口。半乳糖低聚糖（GOS）是一种已被证明可以缓解乳糖不耐受症状并调节肠道微生物群、促进有益微生物生长的益生元。我们假设肠道细菌利用 GOS 的机制是可变的，这会影响功效和反应，而且这种差异发生在菌株水平上。本研究旨在确定人类来源的菌株代谢 GOS 的机制。尽管菌株之间的整体序列同一性（>95%）很高，但菌株之间的碳水化合物利用成分（包括转运蛋白、降解酶和转录调节）存在差异。生理和转录组学分析显示，菌株之间的碳水化合物代谢谱和 GOS 利用存在明显差异。确定了一个负责 GOS 利用的假定操纵子，并通过 6-磷酸-β-半乳糖苷酶的遗传破坏对其进行了特征描述，该酶在 GOS 利用中起关键作用。我们的研究结果强调了在选择益生菌和合生菌以缓解包括乳糖不耐受在内的胃肠道疾病症状时，特定细菌代谢的重要性。
