Firrman Jenni, Deyaert Stef, Mahalak Karley K, Liu LinShu, Baudot Aurélien, Joossens Marie, Poppe Jonas, Cameron Simon J S, Van den Abbeele Pieter
United States Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, Dairy and Functional Foods Research Unit, 600 East Mermaid Lane, Wyndmoor, PA 19462, USA.
Cryptobiotix, Technologiepark-Zwijnaarde 82, 9052 Gent, Belgium.
Nutrients. 2024 Dec 31;17(1):151. doi: 10.3390/nu17010151.
The human gut microbiota develops in concordance with its host over a lifetime, resulting in age-related shifts in community structure and metabolic function. Little is known about whether these changes impact the community's response to microbiome-targeted therapeutics. Providing critical information on this subject, faecal microbiomes of subjects from six age groups, spanning from infancy to 70-year-old adults (n = six per age group) were harvested. The responses of these divergent communities to treatment with the human milk oligosaccharide 2'-fucosyllactose (2'FL), fructo-oligosaccharides (FOS), and lactose was investigated using the SIFR technology that employs bioreactor fermentation and is validated to be predictive of clinical findings. Additionally, it was evaluated whether combining faecal microbiomes of a given age group into a single pooled microbiome produced similar results as the individual microbiomes.
First, marked age-dependent changes in community structure were identified. levels strongly declined as age increased, and species composition was age-dependent: , and were most prevalent for breastfed infants, toddlers/children, and adults, respectively. Metabolomic analyses (LA-REIMS) demonstrated that these age-dependent differences particularly impacted treatment effects of 2'FL (more than FOS/lactose). Further analysis revealed that while 2'FL enhanced production of short-chain fatty acids (SCFAs) and exerted potent bifidogenic effects, regardless of age, the specific species enhanced by 2'FL, as well as subsequent cross-feeding interactions, were highly age-dependent. Furthermore, single-pooled microbiomes produced results that were indicative of the average treatment response for each age group. Nevertheless, pooled microbiomes had an artificially high diversity, thus overestimating treatment responses (especially for infants), did not recapitulate interindividual variation, and disallowed for the correlative analysis required to unravel mechanistic actions.
Age is an important factor in shaping the gut microbiome, with the dominant taxa and their metabolites changing over a lifetime. This divergence affects the response of the microbiota to therapeutics, demonstrated in this study using 2'FL. These results evidence the importance of screening across multiple age groups separately to provide granularity of how therapeutics impact the microbiome and, consequently, human health.
人类肠道微生物群在其宿主的一生中与其共同发展，导致群落结构和代谢功能出现与年龄相关的变化。关于这些变化是否会影响群落对以微生物群为靶点的治疗方法的反应，目前知之甚少。为了提供关于这个问题的关键信息，我们收集了六个年龄组受试者的粪便微生物群，年龄范围从婴儿期到70岁的成年人（每个年龄组n = 6）。使用采用生物反应器发酵且经验证可预测临床结果的SIFR技术，研究了这些不同群落对人乳低聚糖2'-岩藻糖基乳糖（2'FL）、低聚果糖（FOS）和乳糖治疗的反应。此外，还评估了将给定年龄组的粪便微生物群合并成一个单一的混合微生物群是否会产生与个体微生物群相似的结果。
首先，确定了群落结构中明显的年龄依赖性变化。随着年龄的增加， 水平急剧下降，并且 物种组成具有年龄依赖性： 、 和 分别在母乳喂养的婴儿、幼儿/儿童和成年人中最为普遍。代谢组学分析（LA-REIMS）表明，这些年龄依赖性差异尤其影响2'FL的治疗效果（比FOS/乳糖更明显）。进一步分析表明，虽然2'FL无论年龄如何都能增强短链脂肪酸（SCFA）的产生并发挥强大的双歧杆菌生成作用，但2'FL增强的特定 物种以及随后的交叉喂养相互作用具有高度的年龄依赖性。此外，单一混合微生物群产生的结果表明了每个年龄组的平均治疗反应。然而，混合微生物群具有人为的高多样性，因此高估了治疗反应（尤其是对婴儿），没有概括个体间的差异，并且不允许进行揭示作用机制所需的相关分析。
年龄是塑造肠道微生物群的一个重要因素，主要的分类群及其代谢产物在一生中都会发生变化。这种差异影响了微生物群对治疗方法的反应，本研究使用2'FL证明了这一点。这些结果证明了分别对多个年龄组进行筛查的重要性，以提供治疗方法如何影响微生物群进而影响人类健康的详细信息。
