Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

Aging and serum MCP-1 are associated with gut microbiome composition in a murine model
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DOI:
10.7717/peerj.1854/fig-2
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发表时间:
2016-03
期刊:
影响因子:
2.7
通讯作者:
Melissa N. Conley;C. Wong;Kyle M Duyck;N. Hord;E. Ho;T. Sharpton
Melissa N. Conley;C. Wong;Kyle M Duyck;N. Hord;E. Ho;T. Sharpton
中科院分区:
生物学3区
文献类型:
--
作者:
Melissa N. Conley;C. Wong;Kyle M Duyck;N. Hord;E. Ho;T. Sharpton

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导言。年龄是人类主要慢性疾病的主要危险因素,包括心血管疾病、癌症、2型糖尿病和神经退行性疾病。慢性、低级别的全身炎症与衰老和免疫衰老的进展有关。免疫衰老可能在与年龄相关的慢性疾病的发展过程中发挥重要作用,以及广泛观察到的伴随这一过程而产生的炎性介质增加的现象,称为“炎症”。虽然已经证明肠道微生物群和免疫系统相互作用,但肠道微生物群和年龄之间的关系仍有待明确,特别是在炎症的背景下。我们研究的目的是在C57BL/6小鼠模型中阐明年龄、肠道微生物组和促炎标志物血清MCP-1之间的关系。结果。我们使用16S rRNA基因测序来描述与幼年和老年小鼠相关的粪便微生物区系的组成。我们的分析确定了微生物组结构和小鼠年龄之间的关联,并揭示了特定的分类群组,其丰富度在幼鼠和老年鼠之间分层。这包括瘤胃球菌科、梭菌科和肠杆菌科。我们还分析了每只小鼠的促炎血清MCP-1水平,发现老年小鼠的血清MCP-1水平升高,这是一种与炎症相一致的表型。强大的相关性测试确定了几个分类群,它们在微生物群中的丰度与血清MCP-1状态有关,表明它们可能与小鼠免疫系统相互作用。我们发现,在分类学上相似的生物体可以表现出与宿主免疫系统不同的、甚至相反的关联模式。我们还发现,许多与血清MCP-1相关的OTU按年龄对个体进行分层。讨论。我们的结果表明,肠道微生物组组成与年龄和促炎标志物-血清MCP-1有关。年龄、肠道微生物组中特定类群的相对丰度与小鼠血清MCP-1状态之间的相关性表明,肠道微生物组可能在与年龄相关的炎症过程中发挥调节作用。这些发现需要进一步研究与炎症表型相关的分类群,以及肠道微生物群在老年人健康状况和免疫功能中的作用。
Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging.” While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.