Background

The number of people above the age of 60 years is raising world-wide being associated with an increase in the prevalence of aging-associated impairments and even diseases. Recent studies suggest that aging is associated with alterations in bacterial endotoxin levels and that these changes may add to low-grade inflammation, the so-called ‘inflammaging’, and aging-associated liver degeneration. However, mechanisms involved, and especially, the interaction of intestinal microbiota and barrier in the development of aging-associated inflammation and liver degeneration have not been fully understood.

Objective

The aim of the present study was to determine if intestinal microbiota composition changes with age and if these alterations are associated with changes of markers of intestinal barrier function and the development of inflammation and liver degeneration.

Methods

Blood, liver, small and large intestinal tissue of male 2-, 15-, 24- and 30-months old C57BL/6 mice fed standard chow were obtained. Intestinal microbiota composition, expression levels of antimicrobial peptides in small intestine and markers of intestinal barrier function were measured. Furthermore, indices of liver damage, inflammation and expression levels of lipopolysaccharide binding protein (Lbp) as well as of toll-like receptors (Tlr) 1-9 in liver tissue were assessed.

Results

Pairwise comparisons of the microbial community in the small intestine showed differences between 2- and 24-, 15- and 24-, as well as 15- and 30-months old animals while Shannon’s diversity, species richness and evenness indexes did not differ in both small and large intestine, respectively, between age groups. Concentrations of nitric oxide were significantly lower in small intestine of 15-, 24- and 30-months old mice compared to 2-months old mice while mRNA expression of the antimicrobial peptides defensin alpha 1 and lysozyme 1 was unchanged. In contrast, in liver tissue, older age of animals was associated with increasing inflammation and the development of fibrosis in 24- and 30-months old mice. Numbers of inflammatory foci and neutrophils in livers of 24- and 30-months old mice were significantly higher compared to 2-months old mice. These alterations were also associated with higher endotoxin levels in plasma as well as an increased mRNA expression of Lbp and Tlr1, Tlr2, Tlr4, Tlr6 and Tlr9 in livers in older mice.

Conclusion

Despite no consistent and robust changes of microbiota composition in small and/or large intestine of mice of different age were observed, our data suggest that alterations of markers of intestinal barrier function in small intestine are associated with an induction of several Tlrs and beginning hepatic inflammation in older mice and increase with age.

中文翻译：

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微生物群分析与衰老相关的炎症和肝变性

背景

60岁以上的人口数量在世界范围内正在增加，与衰老相关的障碍甚至疾病的患病率增加有关。最近的研究表明，衰老与细菌内毒素水平的变化有关，并且这些变化可能会加重低度炎症，所谓的“发炎”以及与衰老相关的肝变性。然而，与衰老相关的炎症和肝变性的发展中涉及的机制，尤其是肠道菌群与屏障的相互作用尚不完全清楚。

客观的

本研究的目的是确定肠道菌群组成是否随年龄变化，以及这些变化是否与肠道屏障功能标志物的变化以及炎症和肝变性的发展有关。

方法

获得了用标准饲料喂养的2、15、24、30个月大的雄性C57BL / 6小鼠的血液，肝脏，小肠和大肠组织。测量肠道菌群组成，小肠中抗菌肽的表达水平以及肠屏障功能的标志物。此外，评估了肝组织中肝损伤，炎症和脂多糖结合蛋白（Lbp）以及toll样受体（Tlr）1-9的表达水平的指标。

结果

小肠中微生物群落的成对比较显示2月龄和24月龄，15月龄24和15个月龄和30个月龄动物之间存在差异，而香农的多样性，物种丰富度和均匀度指数在这两个方面均没有差异在年龄段之间分别是小肠和大肠。与2个月大的小鼠相比，15个月，24个月和30个月大小鼠的小肠中一氧化氮的浓度显着降低，而抗菌肽防御素α1和溶菌酶1的mRNA表达未改变。相反，在肝脏组织中，动物的年龄增加与24个月和30个月大的小鼠的炎症增加以及纤维化的发展有关。与2个月大的小鼠相比，24个月和30个月大的小鼠肝脏中炎性灶和中性粒细胞的数量显着更高。老年小鼠肝脏中的Lbp和Tlr1，Tlr2，Tlr4，Tlr6和Tlr9。

结论

尽管未观察到不同年龄小鼠的小肠和/或大肠中微生物群组成的一致而稳健的变化，但我们的数据表明，小肠中肠屏障功能标志物的改变与几种Tlrs的诱导和开始的肝炎有关在年长的老鼠中，并随着年龄的增长而增加。