Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
Int J Cardiol. 2024 Feb 1;396:131554. doi: 10.1016/j.ijcard.2023.131554. Epub 2023 Oct 22.
There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity.
This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances.
Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE.
Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.
蛋白丢失性肠病（PLE）是法洛四联症根治术后的一种并发症，目前尚无预测其发病或活动的生物标志物。本研究旨在鉴定活动期 PLE 患者的肠道微生物群组成，并探讨其与 PLE 活动的关系。
本多中心病例对照研究纳入了法洛四联症根治术后发生 PLE（n=16）和未发生 PLE（非 PLE；n=20）的患者。PLE 患者在血清白蛋白水平≥3 g/dL 维持>1 年者纳入缓解期 PLE 组（n=9），未达到该水平者纳入活动期 PLE 组（n=7）。采用 QIIME2 管道对粪便样本的 16S rRNA 基因进行测序分析。采用基于非加权 UniFrac 距离的主坐标分析评估 alpha（Shannon 和 Faith 的系统发育多样性指数）和 beta 多样性。
与缓解期 PLE 组（q=0.028 和 0.025）和非 PLE 组（q=0.028 和 0.017）相比，活动期 PLE 组的 Shannon 和 Faith 的系统发育多样性指数较低。β多样性分析显示，活动期 PLE 组与其他两组之间的微生物群组成存在差异。线性判别效应量分析显示，活动期 PLE 患者与缓解期 PLE 患者的双歧杆菌和 Granulicatella 属以及瘤胃球菌属 Ruminococcus 的相对丰度存在差异。
活动期 PLE 患者存在肠道微生物群失调。肠道微生物群组成的变化和多样性的降低可能与 PLE 的严重程度有关。
