Xie Jiaojiao, Kim Taewan, Liu Zhongmao, Panier Hunter, Bokoliya Suresh, Xu Ming, Zhou Yanjiao
The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
mSystems. 2025 Jun 17;10(6):e0160124. doi: 10.1128/msystems.01601-24. Epub 2025 May 30.
The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.
The gut microbiome is a key hallmark of aging. Fecal microbiota transplantation (FMT) using young microbiota represents a novel rejuvenation strategy to delay aging. Our study provides compelling evidence that transplanting microbiota from young mice significantly improved grip strength, frailty, and body composition in aged recipient mice. At the molecular level, FMT improved aging-related metabolic markers in the gut and circulation. Additionally, FMT from young microbiota rejuvenated the amygdala of the aged brain by downregulating inflammatory pathways. This study highlights the importance of metabolic reprogramming via young microbiota FMT in improving physical and metabolic health in elderly recipients.
肠道微生物群在一生中不断演变，并对衰老过程产生重大影响。针对肠道微生物群是延缓衰老以及与衰老相关的身心衰退的一条新途径。然而，微生物群调节衰老过程的潜在机制，特别是与年龄相关的身体和行为变化，尚未完全了解。我们将年轻或年老雄性供体小鼠的粪便微生物群移植（FMT）到年老雄性受体小鼠体内。接受年轻微生物群移植的年老受体比接受年老微生物群移植的年老受体具有更高的α多样性。与接受年老微生物群移植相比，接受年轻微生物群移植可降低年老受体的体重并防止脂肪堆积。接受年轻微生物群移植还降低了年老受体的虚弱程度，增加了握力，并减轻了抑郁和焦虑样行为。与观察到的身体变化一致，对血清和粪便进行的非靶向代谢组学分析表明，接受年轻微生物群移植可降低年老受体中与年龄相关的长链脂肪酸水平并增加氨基酸水平。对大脑杏仁核进行的批量RNA测序分析表明，接受年轻微生物群移植可下调年老受体中的炎症途径并上调氧化磷酸化。我们的结果表明，接受年轻微生物群移植对与年龄相关的身体成分、虚弱程度和心理行为具有重大积极影响。这些影响与宿主外周脂质和氨基酸代谢的变化以及大脑中神经炎症和能量利用的转录调控有关。
肠道微生物群是衰老的一个关键标志。使用年轻微生物群进行粪便微生物群移植（FMT）是一种延缓衰老的新型恢复活力策略。我们的研究提供了令人信服的证据，表明移植年轻小鼠的微生物群可显著改善老年受体小鼠的握力、虚弱程度和身体成分。在分子水平上，FMT改善了肠道和循环中与衰老相关的代谢标志物。此外，来自年轻微生物群的FMT通过下调炎症途径使老年大脑的杏仁核恢复活力。这项研究强调了通过年轻微生物群FMT进行代谢重编程对改善老年受体的身体和代谢健康的重要性。
