Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.
Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.
复制标题
与衰老相关的肠道微生物组毒力能力增强导致脓毒症严重程度。
DOI：
10.1128/mbio.00052-23
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发表时间：
2023-06-27
期刊：
影响因子：
6.4
通讯作者：
Schmidt, Eric P.
中科院分区：
文献类型：
--
作者：
Colbert, James F.;Kirsch, Joshua M.;Erzen, Christopher L.;Langouet-Astrie, Christophe J.;Thompson, Grace E.;McMurtry, Sarah A.;Kofonow, Jennifer M.;Robertson, Charles E.;Kovacs, Elizabeth J.;Sullivan, Ryan C.;Hippensteel, Joseph A.;Sawant, Namrata V.;De Nisco, Nicole J.;McCollister, Bruce D.;Schwartz, Robert S.;Horswill, Alexander R.;Frank, Daniel N.;Duerkop, Breck A.;Schmidt, Eric P.
先前的研究重点关注宿主因素作为老年人脓毒症相关发病率和死亡率夸大的中介因素。然而，这种对宿主的关注未能找到改善老年人脓毒症结局的治疗方法。我们假设，老年人群对脓毒症的易感性增加不仅是宿主的功能，而且反映了与长寿相关的肠道病原体毒力的变化。我们利用肠道微生物群诱导的实验性脓毒症的两种互补模型，将衰老的肠道微生物群确定为疾病严重程度加剧的关键病理生理驱动因素。对这些多微生物细菌群落的进一步小鼠和人类研究表明，年龄仅与生态组成的微妙变化有关，而且与基因组毒力因子过多有关，这些因子对宿主免疫逃避产生功能性影响。
Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion.
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