Graspeuntner Simon, Lupatsii Mariia, van Zandbergen Vera, Dammann Marie-Theres, Pagel Julia, Nguyen Duc Ninh, Humberg Alexander, Göpel Wolfgang, Herting Egbert, Rupp Jan, Härtel Christoph, Fortmann Ingmar
Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, Germany.
Infection. 2024 Nov 14. doi: 10.1007/s15010-024-02396-6.
We hypothesized that previously healthy infants < 90 days of age with late-onset sepsis (LOS) have disturbances of the gut microbiome with yet undefined specific immunological patterns.
We performed a prospective single-center convenience sample study between January 2019 and July 2021 in a case-control design. Routine diagnostics included conventional cultures (blood, cerebrospinal fluid, urine), PCRs and inflammatory markers in infants aged < 90 days with clinical LOS. We additionally analyzed blood lymphocyte subsets including CD4 + CD25 + forkhead box protein (FoxP3) Tregs and performed 16 S rRNA sequencing of stool samples, both compared to age-matched healthy controls. Results were adjusted for potential confounders that may influence microbial composition.
51 infants with fever and clinical LOS were enrolled. Bacterial sepsis was diagnosed in n = 24 (47.1%) and viral infection in n = 13 (25.5%) infants, whereas in 14 (27.3%) infants the cause of fever remained undetermined. When compared to healthy controls, the gut microbiome of LOS infants at disease onset was characterized by a shift in community composition, specifically, decreased abundance of B. longum and an increase of Bacteroidia spp. Intriguingly, the abundance of B. longum negatively correlated with the frequency of blood CD4-positive cells in healthy controls but not in infants with LOS. At one year of age, we observed microbiome differences in infants with history of LOS when compared to healthy controls, such as an increased gut microbial diversity.
Our data suggest potential signatures of the microbiome-immunity interplay in infants with LOS, which should be investigated further as possible targets for prevention.
我们推测，先前健康的90日龄以下晚发性败血症（LOS）婴儿存在肠道微生物群紊乱，且具有尚未明确的特定免疫模式。
我们在2019年1月至2021年7月期间进行了一项前瞻性单中心便利样本研究，采用病例对照设计。常规诊断包括对90日龄以下临床诊断为LOS的婴儿进行常规培养（血液、脑脊液、尿液）、聚合酶链反应（PCR）和炎症标志物检测。我们还分析了血液淋巴细胞亚群，包括CD4 + CD25 + 叉头框蛋白（FoxP3）调节性T细胞，并对粪便样本进行了16S核糖体RNA测序，两者均与年龄匹配的健康对照进行比较。对可能影响微生物组成的潜在混杂因素进行了结果调整。
纳入了51例发热且临床诊断为LOS的婴儿。24例（47.1%）婴儿诊断为细菌性败血症，13例（25.5%）婴儿诊断为病毒感染，而14例（27.3%）婴儿的发热原因仍未确定。与健康对照相比，LOS婴儿发病时的肠道微生物群特征是群落组成发生变化，具体表现为长双歧杆菌丰度降低，拟杆菌属丰度增加。有趣 的是，长双歧杆菌的丰度与健康对照中血液CD4阳性细胞的频率呈负相关，但在LOS婴儿中并非如此。在1岁时，我们观察到有LOS病史的婴儿与健康对照相比，其微生物群存在差异，如肠道微生物多样性增加。
我们的数据表明，LOS婴儿中微生物群与免疫相互作用存在潜在特征，应进一步研究将其作为可能的预防靶点。
