Association of resistome abundance with hyperuricaemia in elderly individuals: a metagenomics study

Zhiyang Liu, Yingbo Shen, Yulin Fu, Da Sun, Liang Li, Ziquan Lv
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Abstract

Hyperuricaemia (HUA), one of chronic diseases, has an increased prevalence and is related to diseases such as gout, arthritis, infectious diseases, etc. Antimicrobial resistance (AMR) in the gut is considered as an atypical chronic disease, and poses risk to human health. The gut microbiome has been proved to be a reservoir for AMR and play an important role in HUA patients. The microbial characteristics of the gut in individuals with HUA have been previously explored, however, the characteristics of the resistome in individuals with HUA have remained largely unexplored.Thus, we investigated the landscape of the AMR in individuals with HUA and without HUA, and the potentially influential factors in a case-control study using metagenomics-based approaches.We found that drinking juice and abnormal stool were risk factors associated with HUA. The taxonomic diversity of gut microbiota in individuals with HUA was lower than that in non-HUA individuals. Notably, a higher abundance and diversity of the resistome (entire antimicrobial resistance genes) was observed in individuals with HUA (median: 1.10 vs. 0.76, P = 0.039, U-test), especially in tetracycline resistance genes (median: 0.46 vs. 0.20, P < 0.001, U-test), which are associated with more complex mobile genetic elements (MGEs) in individuals with HUA. Furthermore, we found that a higher abundance of the resistome was positively correlated with uric acid (UA) levels and affected by several host-associated factors (mainly dietary habits). Specifically, pork consumption and the consumption of root and tuber vegetables were identified as contributing factors. We also found a higher abundance of virulence genes (VGs), mostly related to adherence, antimicrobial activity, competitive advantage, and exoenzymes, in the gut microbial community of individuals with HUA.All findings revealed higher activity of the resistome and pathogenicity of the microbiota in individuals with HUA, indicating a higher health risk in the elderly HUA population.
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抗原组丰度与老年人高尿酸血症的关系:一项元基因组学研究
高尿酸血症(HUA)是慢性疾病之一,发病率越来越高,并与痛风、关节炎、传染病等疾病有关。肠道中的抗菌药耐药性(AMR)被认为是一种非典型慢性疾病,对人类健康构成风险。肠道微生物组已被证明是 AMR 的储存库,在 HUA 患者中发挥着重要作用。因此,我们在一项病例对照研究中,利用基于元基因组学的方法调查了HUA患者和非HUA患者的AMR状况,以及潜在的影响因素。我们发现,喝果汁和大便异常是与 HUA 相关的风险因素。HUA 患者肠道微生物群的分类多样性低于非 HUA 患者。值得注意的是,在HUA患者中观察到抗性基因组(整个抗菌素抗性基因)的丰度和多样性更高(中位数:1.10 vs. 0.76,P = 0.039,U检验),尤其是四环素抗性基因(中位数:0.46 vs. 0.20,P < 0.001,U检验),这与HUA患者体内更复杂的移动遗传因子(MGEs)有关。此外,我们还发现,较高的抗性基因组丰度与尿酸(UA)水平呈正相关,并受几个宿主相关因素(主要是饮食习惯)的影响。具体来说,猪肉消费和块根及块茎蔬菜消费被认为是诱因。我们还发现,在HUA患者的肠道微生物群落中,毒力基因(VGs)的丰度较高,主要与粘附性、抗菌活性、竞争优势和外酶有关。所有研究结果均显示,HUA患者的抗药性基因组活性较高,微生物群的致病性也较高,这表明HUA老年人群的健康风险较高。
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