School of Microbiology, University College Cork, Cork, Ireland.
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Gut Microbes. 2023 Dec;15(2):2282796. doi: 10.1080/19490976.2023.2282796. Epub 2023 Nov 27.
Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of and . The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of . S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.
人类衰老的特征是肠道微生物组改变和与虚弱发生相关的肠道共生物种的差异丧失。补充培养的共生菌株以补充丢失的分类群可能有助于健康衰老。为了研究整个微生物组和管理菌株之间的相互作用，我们将脆弱或健康老年人的肠道微生物群移植到无菌小鼠中。我们用我们在之前的研究中通过分析健康老年人确定的特定分类群（“S7”）补充脆弱供体受体组，其丰度与促进健康的饮食干预相关。在移植后 5 周，脆弱供体受体组和健康供体受体组的微生物群组成存在差异。在接受健康供体移植的小鼠中，粪便乙酸盐水平在 4 周后显著高于接受脆弱供体移植的小鼠。然而，在接受单次剂量来自健康和脆弱供体的微生物群移植的受体小鼠中，并未复制脆弱相关表型。5 种 S7 种成功定植于无菌小鼠，相对丰度较高的为 和 。5 种 S7 种在无菌小鼠中的定植增加了粪便乙酸盐水平，降低了结肠通透性和血浆 TNF-ɑ浓度。在脆弱微生物群受体小鼠中补充 S7 并没有增加 alpha 多样性，但显著增加了 的丰度。S7 补充显示了改善脆弱微生物群受体小鼠空间参考记忆的潜力。总之，这些数据突出了在无菌小鼠模型中移植老年微生物群的挑战，但通过管理与健康衰老相关的人工肠道微生物群联合体，为改善脆弱老年患者的肠道微生物群提供了希望。
