Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510030, P. R. China.
College of Food Science, South China Agricultural University, Guangzhou, Guangdong, 510630, P. R. China.
Food Funct. 2024 Apr 22;15(8):3993-4009. doi: 10.1039/d3fo05282f.
Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased and increased , , and . Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.
衰弱是一种复杂的老年综合征，严重阻碍了实现“健康老龄化”的目标。越来越多的证据表明肠道微生物群、全身炎症和疾病之间存在联系。然而，目前尚不清楚针对肠道菌群的干预措施是否能有效改善衰弱。我们的研究涉及无菌（GF）小鼠的粪便微生物群移植（FMT）实验，将这些小鼠分为三组：一组接受健康老年人供体的移植（HF 组），一组衰弱患者（FF 组），和 FF 组补充 BFS1243（FFL 组）。我们的研究结果表明，FF 组的肠道微生物群发生了显著变化，与 HF 组相比，其特征是减少，增加，，和。同时，氨基酸和 SCFAs 减少，BFS1243 部分缓解了这些变化。FF 组的炎症标志物（包括 PGE2、CRP 和 TNF-α）表达上调，而 irisin 表达下调，BFS1243 治疗部分缓解了这些变化。此外，BFS1243 改善了 FF 小鼠的肠道屏障完整性和体力耐力。相关性分析显示，产生 SCFA 的物种与赖氨酸和丁酸等代谢物与促炎因子呈负相关。总之，我们的研究明确表明，老年人肠道微生物群的改变可能导致身体衰弱，这可能是由于对肠道屏障和促炎状态的不利影响。这些发现强调了肠道微生物组调节作为治疗衰弱的临床策略的潜力。
