Geese Theresa, Dempfle Astrid
Institute of Medical Informatics and Statistics, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany.
Comput Struct Biotechnol J. 2025 May 10;27:1945-1961. doi: 10.1016/j.csbj.2025.05.005. eCollection 2025.
The gut microbiome's role in inflammatory bowel disease (IBD) is well-established, but capturing its complexity is challenging. Network analysis offers a valuable approach, but selecting suitable measures is crucial. This study examines the sensitivity of network properties to abundance variations. It evaluates whether these properties reflect the microbiome in IBD or are too sensitive to variability from e.g. laboratory conditions or intra-individual changes.
Using genetically unrelated individuals from the KINDRED cohort (IBD n = 522, healthy controls n = 365) and the PRISM cohort (IBD n = 42, healthy controls n = 42), microbial networks were constructed with genera as nodes and significant pairwise correlations as edges, separately for IBD patients and controls. Important IBD-related nodes, identified through centrality measures, and non-disease-related nodes were varied in abundance ( ± 30 %), and networks were re-constructed and compared with initial networks regarding local and global properties.
Network properties in IBD were sensitive to abundance variations, with small and large changes producing similar effects. Sensitivity to increasing read counts of disease-related and non-disease-related genera was similar. Local properties showed magnitude-dependent changes of up to 50 % in response to the depletion of disease-related genera, relative to no modification applied, and an almost binary sensitivity pattern when modifying non-disease-related genera. Global case network properties changed less than 10 % in most settings, potentially indicating a certain stability of dysbiosis.
Caution is needed with network-based approaches, as even small variations, stemming from sources of microbiome variability, can affect results and reproducibility. The relatively stable dysbiosis in IBD could pose challenges for microbiome-directed therapies.
肠道微生物群在炎症性肠病（IBD）中的作用已得到充分证实，但要全面了解其复杂性仍具有挑战性。网络分析提供了一种有价值的方法，但选择合适的指标至关重要。本研究探讨了网络特性对丰度变化的敏感性。评估这些特性是否反映了IBD中的微生物群，还是对例如实验室条件或个体内变化的变异性过于敏感。
使用来自KINDRED队列（IBD患者n = 522，健康对照n = 365）和PRISM队列（IBD患者n = 42，健康对照n = 42）的非亲缘个体，分别以属为节点、显著的成对相关性为边构建IBD患者和对照的微生物网络。通过中心性度量确定的重要IBD相关节点和非疾病相关节点的丰度发生变化（±30%），重新构建网络，并与初始网络在局部和全局特性方面进行比较。
IBD中的网络特性对丰度变化敏感，无论变化大小，产生的影响相似。对疾病相关和非疾病相关属的读数增加的敏感性相似。相对于未进行修改，局部特性显示，疾病相关属的减少会导致高达50%的幅度依赖性变化，而修改非疾病相关属时则呈现几乎二元的敏感性模式。在大多数情况下，全局病例网络特性的变化小于10%，这可能表明菌群失调具有一定的稳定性。
基于网络的方法需要谨慎使用，因为即使是微生物群变异性来源产生的微小变化，也可能影响结果和可重复性。IBD中相对稳定的菌群失调可能对微生物群导向疗法构成挑战。
