Fecal multi-omics analysis reveals diverse molecular alterations of gut ecosystem in COVID-19 patients.
Fecal multi-omics analysis reveals diverse molecular alterations of gut ecosystem in COVID-19 patients.
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粪便多组学分析揭示了 COVID-19 患者肠道生态系统的多种分子变化
DOI：
10.1016/j.aca.2021.338881
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发表时间：
2021-10-02
影响因子：
6.2
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
He F;Zhang T;Xue K;Fang Z;Jiang G;Huang S;Li K;Gu Z;Shi H;Zhang Z;Zhu H;Lin L;Li J;Xiao F;Shan H;Yan R;Li X;Yan Z
肠道生态系统对宿主的生理和健康有着深远的影响。在COVID-19患者中经常观察到胃肠道（GI）症状。与其他器官相比，肠道抗病毒反应可导致更复杂的免疫反应，因为肠道微生物群与宿主免疫之间存在相互作用。然而，在COVID-19对肠道分子谱和肠道微生物组的影响方面仍存在很大的知识空白，阻碍了我们对SARS-CoV-2发病机制和COVID-19治疗的全面理解。我们进行了纵向粪便多组学分析，以系统地研究COVID-19中肠道生态系统的分子表型组学改变。COVID-19肠道蛋白质组的特征是免疫、蛋白质水解和氧化还原稳态受到干扰。参与中性粒细胞脱粒和迁移的蛋白质的表达和糖基化被抑制，而蛋白酶的表达和糖基化被上调。IG重链可变区下调，伊加重链恒定区、IgGFc结合蛋白和J链的总体糖基化受到聚糖特异性变异的抑制。有益肠道细菌减少，细菌衍生的有害代谢物富集，可能与多种类型的疾病（如乙基葡萄糖醛酸苷）相关。IG重链可变区的减少可能有助于某些拟杆菌属物种的增加。许多基于C17-鞘氨醇的细菌神经酰胺脂质在COVID-19中下调。在许多情况下，肠道表型在症状发作后两个月没有恢复。我们的研究表明，肠道分子谱受到广泛干扰，可能在COVID-19症状的发展中发挥作用。我们的研究结果还强调，需要持续研究COVID-19恢复过程中的长期肠道分子和微生物变化。将肠道生态系统视为潜在目标可以为管理这种疾病提供有价值的方法。
Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19. We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset. Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.
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影响因子：
4.4
作者：
Gurdeep Singh, Robbert;Tanca, Alessandro;Mesuere, Bart
通讯作者：
Mesuere, Bart
95例SARS-CoV-2胃肠道症状
影响因子：
24.5
作者：
Lin, Lu;Jiang, Xiayang;Shan, Hong
通讯作者：
Shan, Hong
影响因子：
16.6
作者：
Johnson, Elizabeth L.;Heaver, Stacey L.;Ley, Ruth E.
通讯作者：
Ley, Ruth E.
影响因子：
30.3
作者：
Bates, Jennifer M.;Akerlund, Janie;Guillemin, Karen
通讯作者：
Guillemin, Karen
DOI：
10.1126/science.abc6261
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arunachalam PS;Wimmers F;Mok CKP;Perera RAPM;Scott M;Hagan T;Sigal N;Feng Y;Bristow L;Tak-Yin Tsang O;Wagh D;Coller J;Pellegrini KL;Kazmin D;Alaaeddine G;Leung WS;Chan JMC;Chik TSH;Choi CYC;Huerta C;Paine McCullough M;Lv H;Anderson E;Edupuganti S;Upadhyay AA;Bosinger SE;Maecker HT;Khatri P;Rouphael N;Peiris M;Pulendran B
通讯作者：
Pulendran B