Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality.
Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality.
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DOI：
10.1016/j.celrep.2015.08.004
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发表时间：
2015-09-08
期刊：
影响因子：
8.8
通讯作者：
Walker DW
中科院分区：
文献类型：
--
作者：
Clark RI;Salazar A;Yamada R;Fitz-Gibbon S;Morselli M;Alcaraz J;Rana A;Rera M;Pellegrini M;Ja WW;Walker DW
肠道微生物群组成的变化与老年人的衰老和虚弱程度相关。然而，微生物动力学、肠道生理学与年龄相关的变化和机体健康之间的关系仍然知之甚少。在这里，我们发现，以伽马变形菌扩张为特征的肠道微生物群失调与果蝇年龄相关的肠道屏障功能障碍密切相关。事实上，微生物群的变化先于并预测老年果蝇肠道屏障功能障碍的发生。在肠道屏障功能障碍之前发生的微生物组成的变化导致衰老肠道中排泄功能和免疫基因激活的变化。此外，我们发现肠道屏障功能障碍后微生物群组成发生明显变化，导致全身免疫激活和有机体死亡。我们的研究结果表明，微生物群动态的变化可能会导致并预测哺乳动物衰老过程中不同程度的健康下降速度。
Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals.