Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses.

Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses.
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年龄、热量限制和流感感染对小鼠肠道微生物组的影响:年龄相关微生物组变化对流感反应作用的探索性研究。

DOI:
10.3389/fimmu.2017.01164
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发表时间:
2017
影响因子:
7.3
通讯作者:
Haynes L
Haynes L
中科院分区:
医学2区
文献类型:
--
作者:
Bartley JM;Zhou X;Kuchel GA;Weinstock GM;Haynes L

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免疫衰老是指年龄相关的能力下降,以应对感染,如流感(流感)。热量限制是一种已知的减缓许多衰老过程的策略,包括那些涉及免疫系统的过程。最近,随着年龄的增长,微生物组的一些变化已经被描述,而肠道微生物组似乎会影响对流感疫苗接种和感染的反应。考虑到这些因素,我们使用了一个完善的流感感染小鼠模型来探索流感感染、衰老和热量限制对肠道微生物组的影响。在亚致死性流感感染后,检查了年轻、中年和老年热量限制(CR)和自由进食(AL)小鼠。所有小鼠体重减轻10-20%,正如这些早期时间点的预期,不同年龄和饮食组之间的体重减轻相似。细胞因子和趋化因子水平也相似,但IL-1α明显例外,其在老年AL小鼠血清中升高超过5倍,而在老年CR血清中保持不变。在基线和流感感染后4天,年轻、中年和老年AL小鼠的粪便微生物组门丰度谱相似,而在所有三个年龄组中,流感感染后7天变形菌门的增加是明显的。与各年龄组的AL小鼠相比,CR小鼠在所有时间点的变形菌门和疣微菌门丰度均增加。有趣的是,主坐标分析确定饮食对微生物组的影响大于年龄或流感感染。无论年龄大小,体重减轻百分比与变形菌的相对丰度相关,表明流感致病性与变形菌丰度相关。此外,来自拟杆菌门的几种微生物操作分类单位与血清趋化因子/细胞因子相关,而与饮食和年龄无关,这表明流感诱导的全身性炎症和肠道微生物群之间存在相互作用。这些探索性研究强调了热量限制对年轻和老年动物粪便微生物组的影响,以及流感反应和肠道微生物群之间的许多复杂关系。因此,这些初步研究提供了必要的基础,以研究如何利用肠道微生物群的改变来影响随着衰老而下降的免疫反应。
Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome. Young, middle-aged, and aged caloric restricted (CR) and ad lib fed (AL) mice were examined after a sublethal flu infection. All mice lost 10–20% body weight and, as expected for these early time points, losses were similar at different ages and between diet groups. Cytokine and chemokine levels were also similar with the notable exception of IL-1α, which rose more than fivefold in aged AL mouse serum, while it remained unchanged in aged CR serum. Fecal microbiome phyla abundance profiles were similar in young, middle-aged, and aged AL mice at baseline and at 4 days post flu infection, while increases in Proteobacteria were evident at 7 days post flu infection in all three age groups. CR mice, compared to AL mice in each age group, had increased abundance of Proteobacteria and Verrucomicrobia at all time points. Interestingly, principal coordinate analysis determined that diet exerts a greater effect on the microbiome than age or flu infection. Percentage body weight loss correlated with the relative abundance of Proteobacteria regardless of age, suggesting flu pathogenicity is related to Proteobacteria abundance. Further, several microbial Operational Taxonomic Units from the Bacteroidetes phyla correlated with serum chemokine/cytokines regardless of both diet and age suggesting an interplay between flu-induced systemic inflammation and gut microbiota. These exploratory studies highlight the impact of caloric restriction on fecal microbiome in both young and aged animals, as well as the many complex relationships between flu responses and gut microbiota. Thus, these preliminary studies provide the necessary groundwork to examine how gut microbiota alterations may be leveraged to influence declining immune responses with aging.
DOI: 10.18632/aging.100882
发表时间: 2016-04
期刊: Aging
影响因子: --
作者:
Bartley JM;Pan SJ;Keilich SR;Hopkins JW;Al-Naggar IM;Kuchel GA;Haynes L
通讯作者: Haynes L
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期刊: Science (New York, N.Y.)
影响因子: --
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DOI: 10.4049/jimmunol.1101682
发表时间: 2012-02-01
影响因子: 4.4
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发表时间: 2006-11-10
期刊: VACCINE
影响因子: 5.5
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