The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.
The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.
复制标题
肠道宏基因组具有中度至重度哮喘的代谢和抗生素耐药性特征。
DOI：
10.1101/2023.01.03.522677
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kau,AndrewL
中科院分区：
文献类型：
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作者：
Wilson,NaomiG;Hernandez-Leyva,Ariel;Schwartz,DrewJ;Bacharier,LeonardB;Kau,AndrewL
哮喘是一种常见的过敏性呼吸道疾病，与人类早期微生物群的发育有关。婴儿肠道微生物区系的组成和功能都与哮喘风险有关，但老年哮喘患者肠道微生物区系的功能变化仍然是一个重要的知识缺口。在这里，我们对来自59名健康受试者和36名中重度哮喘患者的横断面队列中的95份粪便样本进行了完整的超基因组鸟枪测序，以表征6岁及以上成人和儿童肠道微生物区系的亚基因组。功能同源基因图谱显示，哮喘贡献了元基因组内容变异的2.9%，即使考虑到其他重要的临床人口学特征。差异丰度分析显示，长链脂肪酸(LCFA)代谢途径丰富，此前已被认为与哮喘的气道平滑肌和免疫反应有关。我们还观察到哮喘患者中抗生素耐药基因(ARGs)的丰富程度增加。哮喘队列中几种不同丰富的ARG编码了对大环内酯类抗生素的耐药性，大环内酯类抗生素经常被开给哮喘患者。最后，我们发现在两个队列中ARG和毒力因子(VF)的丰度在两个队列中都是相关的。Arg和VF对在两个队列中同时出现，这表明毒力和抗生素耐药性特征是共同选择的，并在哮喘患者的粪便微生物群中保持。总体而言，我们的结果显示了通过LCFA生物合成基因的功能变化和中重度哮喘患者肠道微生物区系中抗生素耐药性基因的增加，这可能对哮喘的管理和治疗有意义。
Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.