Renk Hanna, Schoppmeier Ulrich, Müller Jennifer, Kuger Vanessa, Neunhoeffer Felix, Gille Christian, Peter Silke
Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University Children's Hospital Tübingen, Tübingen, Germany.
German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.
Front Microbiol. 2025 Jan 15;15:1468842. doi: 10.3389/fmicb.2024.1468842. eCollection 2024.
Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.
We evaluated the intestinal microbial composition of neonates with CHD ( = 13) compared to healthy controls (HC, = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method.
Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera (27%) and (20%). Furthermore, a lower abundance of the genera (8% vs. 14%), (1% vs. 3%), (4% vs. 12%), and (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera (15% vs. 21%) and (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance ([8,2] = 24.9, = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus (50%) in conditions with low SpO2 towards the genus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.
Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.
已知生命早期的肠道微生物群会塑造免疫系统，并在免疫稳态中发挥关键作用。关于先天性心脏病（CHD）婴儿肠道微生物群的组成和动态以及潜在影响因素，人们了解甚少。
我们评估了患有CHD的新生儿（n = 13）与健康对照（HC，n = 30）的肠道微生物组成。通过鸟枪法宏基因组学分析粪便样本。应用不同的统计建模方法来评估影响因素对物种组成变化的影响。对患有CHD的新生儿的微生物组成进行无监督层次聚类，以检测通过“氧可视”（O2C）方法获得的不同聚类与肠道组织氧合和灌注参数之间的关联。
总体而言，患有CHD的新生儿显示肠道核心微生物群以属（27%）和属（20%）为主。此外，与HC相比，CHD中属（8%对14%）、属（1%对3%）、属（4%对12%）和属（8%对23%）的丰度较低。与HC相比，经阴道分娩的CHD患者属（15%对21%）和属（7%对22%）的比例较低，而在剖宫产出生的患者中，根本未发现这些属。在患有CHD的婴儿中，通过多变量方差分析，我们发现氧饱和度（SpO2）对肠道核心微生物群的相对丰度有显著影响（[8,2]=24.9，P = 0.04）。统计建模表明，在低SpO2条件下，微生物群以属（50%）为主，而在高SpO2条件下，微生物群向属（61%）发生了较大比例的转变。我们确定了三个不同的组成微生物聚类，相应的新生儿在肠道血流和整体肠道灌注方面存在显著差异。
CHD新生儿与HC在生命早期肠道微生物群的差异可能与氧水平有关。分娩方式可能会影响微生物群的稳定性。然而，需要进一步研究来评估包括益生菌或粪便移植在内的潜在干预措施对患有CHD的新生儿生命早期微生物群扰动的影响。
