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Abstract：
The gut microbiota plays an essential role in the regulation of the immune system and the etiology of human autoimmune diseases. However, a holistic understanding of the gut bacteriome, mycobiome, and virome in patients with osteoarthritis (OA) remains lacking. Here, we explored the gut microbiotas of 44 OA patients and 46 healthy volunteers via deep whole-metagenome shotgun sequencing of their fecal samples. The gut bacteriome and mycobiome were analyzed using a reference-based strategy. Gut viruses were identified from the metagenomic assembled contigs, and the gut virome was profiled based on 6,567 nonredundant viral operational taxonomic units (vOTUs). We revealed that the gut microbiome (including bacteriome, mycobiome, and virome) of OA patients is fundamentally altered, characterized by a panel of 279 differentially abundant bacterial species, 10 fungal species, and 627 vOTUs. The representative OA-enriched bacteria included Anaerostipes hadrus (GENOME147149), Prevotella sp900313215 (GENOME08259), Eubacterium_E hallii (GENOME000299), and Blautia A (GENOME001004), while Bacteroides plebeius A (GENOME239725), Roseburia inulinivorans (GENOME 001770), Dialister sp900343095 (GENOME075103), Phascolarctobacterium faecium (GENOME233517), and several members of Faecalibacterium and Prevotella were depleted in OA patients. Fungi such as Debaryomyces fabryi (GenBank accession no. GCA_003708665), Candida parapsilosis (GCA_000182765), and Apophysomyces trapeziformis (GCA_000696975) were enriched in the OA gut microbiota, and Malassezia restricta (GCA_003290485), Aspergillus fumigatus (GCA_003069565), and Mucor circinelloides (GCA_010203745) were depleted. The OA-depleted viruses spanned Siphoviridae (95 vOTUs), Myoviridae (70 vOTUs), and Microviridae (5 vOTUs), while 30 Siphoviridae vOTUs were enriched in OA patients. Functional analysis of the gut bacteriome and virome also uncovered their functional signatures in relation to OA. Moreover, we demonstrated that the OA-associated gut bacterial and viral signatures are tightly interconnected, suggesting that they may impact disease together. Finally, we showed that the multikingdom signatures are effective in discriminating the OA patients from healthy controls, suggesting the potential of gut microbiota for the prediction of OA and related diseases. Our results delineated the fecal bacteriome, mycobiome, and virome landscapes of the OA microbiota and provided biomarkers that will aid in future mechanistic and clinical intervention studies. IMPORTANCE The gut microbiome of OA patients was completely altered compared to that in healthy individuals, including 279 differentially abundant bacterial species, 10 fungal species and 627 viral operational taxonomic units (vOTUs). Functional analysis of the gut bacteriome and virome also revealed their functional signatures in relation to OA. We found that OA-associated gut bacterial and viral signatures were tightly interconnected, indicating that they may affect the disease together. The OA patients can be discriminated effectively from healthy controls using the multikingdom signatures, suggesting the potential of gut microbiota for the prediction of OA and related diseases.
摘要：
肠道菌群在免疫系统的调节和人类自身免疫性疾病的病因中起着至关重要的作用。然而,对肠道细菌的整体理解，mycobiome,骨关节炎（OA）患者中仍然缺乏病毒。这里,我们通过对44例OA患者和46例健康志愿者的粪便样本进行深全宏基因组鸟枪测序,对他们的肠道微生物进行了研究.使用基于参考的策略分析肠道细菌组和分枝杆菌组。从宏基因组组装的重叠群中鉴定出肠道病毒，并且基于6,567个非冗余病毒操作分类单位（vOTU）对肠道病毒进行了分析。我们发现肠道微生物组(包括细菌组，mycobiome,OA患者的病毒基因）发生了根本性的改变，以一组279种差异丰富的细菌为特征，10种真菌，和627个vOTU。代表性的富含OA的细菌包括厌氧菌（GENOME147149），Prevotellasp900313215(GENOME08259),真杆菌（GENOME000299），和BlautiaA（GENOME001004），而拟杆菌A（基因组239725），inulinivoransRoseburiainulivorans(GENOME001770),Dialistersp900343095(GENOME075103),屎相抗体(GENOME233517),OA患者的一些Faecalibacterium和Prevotella成员被耗尽。真菌，如德巴酵母(GenBank登录号GCA_003708665),近平滑念珠菌(GCA_000182765),和白针菌(GCA_000696975)富集在OA肠道微生物群中，和马拉色菌(GCA_003290485)，烟曲霉(GCA_003069565),和毛霉（GCA_010203745）被耗尽。OA耗尽的病毒跨越了Siphoviridae（95个vOTU），Myoviridae(70vOTUs),和微病毒科（5个vOTU），而OA患者中富集了30个虹彩病毒科vOTUs。肠道细菌组和病毒体的功能分析也揭示了它们与OA相关的功能特征。此外，我们证明了与OA相关的肠道细菌和病毒特征是紧密相连的，表明它们可能一起影响疾病。最后,我们表明，多王国签名在区分OA患者与健康对照中是有效的，提示肠道菌群对OA和相关疾病的预测潜力。我们的结果描绘了粪便细菌群，mycobiome,和OA微生物群的病毒景观，并提供了生物标志物，将有助于未来的机制和临床干预研究。重要性与健康个体相比，OA患者的肠道微生物组完全改变，包括279种差异丰富的细菌，10种真菌和627种病毒操作分类单位(vOTU)。肠道细菌组和病毒体的功能分析也揭示了它们与OA相关的功能特征。我们发现与OA相关的肠道细菌和病毒特征紧密相关，表明它们可能一起影响疾病。使用多王国签名可以有效地将OA患者与健康对照区分开来，提示肠道菌群对OA和相关疾病的预测潜力。
