A Multi Omics Approach Unravels Metagenomic and Metabolic Alterations of a Probiotic and Synbiotic Additive in Rainbow Trout (Oncorhynchus Mykiss)

Background Animal protein production is increasingly looking towards microbiome associated services such as the design of new and better probiotic solutions to further improve gut health and production sustainability. Here, we investigate the functional effects of bacteria based pro- and synbiotic feed additives on microbiome associated functions in relation to growth performance in the commercially important rainbow trout (Oncorhynchus mykiss). We combine complementary insights from multiple omics datasets from gut content samples, including 16S bacterial profiling, whole metagenomes, and untargeted metabolomics, to investigate bacterial metagenomic assembled genomes (MAGs) and their molecular interactions with host metabolism. Results Our findings reveal, that (I) feed additives changed the microbiome and that rainbow trout reared with feed additives had a significantly reduced relative abundance of the salmonid related Candidatus Mycoplasma salmoninae in both the mid and distal gut content, (II) genome resolved metagenomics revealed that alterations of microbial arginine biosynthesis and terpenoid backbone synthesis pathways were directly associated with presence of Candidatus Mycoplasma salmoninae, (III) differences in the composition of intestinal microbiota among feed types were directly associated with significant changes of the metabolomic landscape, including lipids and lipid-like metabolites, amino acids, bile acids, and steroid-related metabolites. Conclusion Our results demonstrate how use of multi-omics to investigate complex host-microbiome interactions enable us to better evaluate the functional potential of probiotics compared to studies that only measure overall growth performance or that only characterise the microbial composition in intestinal environments.

研究背景
动物蛋白生产领域正日益转向依托微生物组（microbiome）的相关服务，例如开发新型优质益生菌（probiotic）解决方案，以进一步提升肠道健康与生产可持续性。本研究以商业化养殖的重要物种虹鳟（Oncorhynchus mykiss）为对象，探究基于细菌的益生元、合生元（synbiotic）饲料添加剂对与生长性能相关的微生物组功能的调控效应。我们整合肠道内容物样本的多组学（omics）数据集所提供的互补信息——包括16S细菌谱系分析（16S bacterial profiling）、全宏基因组测序（whole metagenomes）与非靶向代谢组学（untargeted metabolomics）——来探究细菌宏基因组组装基因组（MAGs）及其与宿主代谢的分子互作机制。

研究结果
本研究结果显示：（1）饲料添加剂可改变肠道微生物组，投喂添加剂的虹鳟其中肠与远端肠道内容物中，鲑科鱼类相关候选鲑支原体（Candidatus Mycoplasma salmoninae）的相对丰度显著降低；（2）基因组解析宏基因组学研究显示，微生物精氨酸生物合成与类异戊二烯骨架合成通路的改变，与候选鲑支原体的存在直接相关；（3）不同饲料类型下肠道菌群组成的差异，与代谢组图谱的显著改变直接相关，这些改变涉及脂质及类脂质代谢物、氨基酸、胆汁酸与类固醇相关代谢物。

研究结论
相较于仅测量整体生长性能或仅表征肠道环境微生物组成的研究，本研究结果证实了利用多组学技术探究复杂宿主-微生物组互作，可帮助我们更精准地评估益生菌的功能潜力。