Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute -Microbiome Dynamics, Jena, Germany.
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong S.A.R., China.
Microbiome. 2023 Aug 8;11(1):178. doi: 10.1186/s40168-023-01604-z.
A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure.
Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota's resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting "responders" and "non-responders" independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities.
We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. Video Abstract.
越来越多的证据表明，肠道微生物群与人类健康密切相关。人们已经认识到，以微生物组为导向的干预措施，如饮食和运动，是一种可行且可实现的策略，可以预防疾病和改善人类健康。然而，由于个体间肠道微生物群的个体间差异很大，因此生活方式建议预计对微生物组结构具有不同且高度可变的影响。
在这里，通过对来自 396 名个体在生活方式研究中纵向获得的 1448 个 shotgun 宏基因组样本进行大规模荟萃分析，我们揭示了拟杆菌（Bacteroides stercoris）、普雷沃氏菌（Prevotella copri）和脆弱拟杆菌（Bacteroides vulgatus）作为微生物群抵抗结构变化的标志物，以及芳香族和非芳香族氨基酸生物合成作为微生物组动力学的重要调节剂。我们建立了区分显著的组成变化与正常微生物群波动的标准，并根据其反应水平对个体进行分类。我们进一步开发了一种机器学习模型，用于独立于干预类型预测“应答者”和“非应答者”，在不同种族的外部验证队列中的曲线下面积高达 0.86。
我们在此提出，基于微生物组的分层是可能的，以确定具有高度可塑性或高度抗性微生物结构的个体。确定不会对以重塑肠道微生物群为目标的一般性生活方式治疗干预产生反应的受试者对于确保临床研究的主要终点非常重要。视频摘要。
