Gut Microbes and Health Research Programme, Quadram Institute, Norwich, NR4 7UQ, UK.
Institute of Ophthalmology, University College London, London, EC1V 9EL, UK.
Microbiome. 2022 Apr 29;10(1):68. doi: 10.1186/s40168-022-01243-w.
Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.
Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.
We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.
These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.
晚年肠道微生物群落组成的改变与炎症衰老、组织功能下降以及易患与年龄相关的慢性疾病（包括神经退行性痴呆）有关。在这里，我们检验了这样一个假设，即肠道微生物群的操纵会影响与衰老相关的主要合并症的发展，特别是影响大脑和视网膜的炎症。
我们使用粪便微生物群移植术，交换了年轻（3 个月）、年老（18 个月）和老年（24 个月）小鼠的肠道微生物群。全宏基因组鸟枪法测序和代谢组学用于开发定制分析工作流程，以分析肠道微生物群落组成和代谢潜力的变化。使用蛋白质分析、免疫组织化学和行为测试评估年龄和菌群转移对肠道屏障、视网膜和大脑的影响。
我们表明，年轻或老年小鼠的肠道微生物群落组成谱和丰富的关键物种可以通过 FMT 在年轻和年老小鼠之间成功转移，并且 FMT 调节了由此产生的代谢途径谱。将年老供体微生物群转移到年轻小鼠中，会加速与年龄相关的中枢神经系统（CNS）炎症、视网膜炎症和细胞因子信号，并促进眼部关键功能蛋白的丧失，这些影响与肠道屏障通透性增加一致。相反，这些有害影响可以通过转移年轻供体微生物群来逆转。
这些发现表明，衰老的肠道微生物群会导致肠道-大脑和肠道-视网膜轴的有害变化，这表明微生物调节可能对预防与年龄相关的组织衰退具有治疗益处。视频摘要。
