Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.

中文翻译：

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综合宏基因组分析揭示了与肥胖相关的独特肠道微生物特征

肥胖是一种代谢紊乱，与肠道微生物组成的深刻改变密切相关。然而，肥胖症中肠道微生物组的物种组成和功能变化的动态仍有待全面研究。在这项研究中，我们对多个队列中肥胖和非肥胖个体的宏基因组测序数据进行了荟萃分析，总计 1351 个粪便宏基因组。我们的结果表明，肥胖患者肠道细菌组和病毒组的丰富度和多样性均显着下降。我们鉴定了 38 种细菌，包括真杆菌属 sp.。 CAG：274、瘤胃球菌、真杆菌、Akkermansia muciniphila 以及 1 种古细菌，Methanobrevibacter smithii，在肥胖中发生显着改变。此外，我们观察到五个病毒科的丰度发生了变化：Mesyanzhinovviridae、Chaseviridae、Salasmaviridae、Drexlerviridae 和 Casjensviridae。肠道微生物组的功能分析表明了与肥胖相关的独特特征，并确定齿状瘤胃球菌是肥胖症功能丰富的主要驱动因素，而史密斯甲烷短杆菌、嗜粘蛋白阿克曼氏菌、双循环瘤胃球菌和西氏真杆菌是健康对照组的功能驱动因素。此外，我们的结果表明抗生素抗性基因和细菌毒力因子可能会影响肥胖的发展。最后，我们证明肠道 vOTU 实现了诊断准确性，曲线下面积为 0.766，可区分肥胖与健康对照。我们的研究结果为与肥胖相关的肠道细菌组和病毒组特征提供了全面且普遍的见解，并有可能指导基于微生物组的诊断的发展。