Arzamasov Aleksandr A, Rodionov Dmitry A, Hibberd Matthew C, Guruge Janaki L, Kazanov Marat D, Leyn Semen A, Kent James E, Sejane Kristija, Bode Lars, Barratt Michael J, Gordon Jeffrey I, Osterman Andrei L
Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA.
Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
bioRxiv. 2024 Jul 7:2024.07.06.602360. doi: 10.1101/2024.07.06.602360.
Bifidobacteria are among the earliest colonizers of the human gut, conferring numerous health benefits. While multiple strains are used as probiotics, accumulating evidence suggests that the individual responses to probiotic supplementation may vary, likely due to a variety of factors, including strain type(s), gut community composition, dietary habits of the consumer, and other health/lifestyle conditions. Given the saccharolytic nature of bifidobacteria, the carbohydrate composition of the diet is one of the primary factors dictating the colonization efficiency of strains. Therefore, a comprehensive understanding of bifidobacterial glycan metabolism at the strain level is necessary to rationally design probiotic or synbiotic formulations that combine bacterial strains with glycans that match their nutrient preferences. In this study, we systematically reconstructed 66 pathways involved in the utilization of mono-, di-, oligo-, and polysaccharides by analyzing the representation of 565 curated metabolic functional roles (catabolic enzymes, transporters, transcriptional regulators) in 2973 non-redundant cultured isolates and metagenome-assembled genomes (MAGs). Our analysis uncovered substantial heterogeneity in the predicted glycan utilization capabilities at the species and strain level and revealed the presence of a yet undescribed phenotypically distinct subspecies-level clade within the species. We also identified Bangladeshi isolates harboring unique gene clusters tentatively implicated in the breakdown of xyloglucan and human milk oligosaccharides. Predicted carbohydrate utilization phenotypes were experimentally characterized and validated. Our large-scale genomic analysis considerably expands the knowledge of carbohydrate metabolism in bifidobacteria and provides a foundation for rationally designing single- or multi-strain probiotic formulations of a given bifidobacterial species as well as synbiotic combinations of bifidobacterial strains matched with their preferred carbohydrate substrates.
双歧杆菌是最早定殖于人类肠道的微生物之一，具有众多健康益处。虽然多种菌株被用作益生菌，但越来越多的证据表明，个体对益生菌补充剂的反应可能存在差异，这可能是由于多种因素造成的，包括菌株类型、肠道菌群组成、消费者的饮食习惯以及其他健康/生活方式状况。鉴于双歧杆菌的糖分解特性，饮食中的碳水化合物组成是决定菌株定殖效率的主要因素之一。因此，有必要在菌株水平上全面了解双歧杆菌的聚糖代谢，以便合理设计将细菌菌株与符合其营养偏好的聚糖相结合的益生菌或合生元配方。在本研究中，我们通过分析2973个非冗余培养分离株和宏基因组组装基因组（MAG）中565个经过整理的代谢功能角色（分解代谢酶、转运蛋白、转录调节因子）的表现，系统地重建了66条参与单糖、二糖、寡糖和多糖利用的途径。我们的分析揭示了在物种和菌株水平上预测的聚糖利用能力存在显著异质性，并揭示了在该物种中存在一个尚未描述的表型不同的亚种水平分支。我们还鉴定出孟加拉国分离株含有可能与木葡聚糖和人乳寡糖分解有关的独特基因簇。预测的碳水化合物利用表型通过实验进行了表征和验证。我们的大规模基因组分析大大扩展了双歧杆菌碳水化合物代谢的知识，并为合理设计给定双歧杆菌物种的单菌株或多菌株益生菌配方以及双歧杆菌菌株与其首选碳水化合物底物相匹配的合生元组合提供了基础。
