Lee Chee-Seng, Lin Chia-Ray, Chua Huey-Huey, Wu Jia-Feng, Chang Kai-Chi, Ni Yen-Hsuan, Chang Mei-Hwei, Chen Huey-Ling
Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
JHEP Rep. 2024 Apr 9;6(7):101090. doi: 10.1016/j.jhepr.2024.101090. eCollection 2024 Jul.
BACKGROUND & AIMS: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes.
Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed.
In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of () was significantly lower in patients before and after KPE than in HCs. The abundance of was negatively correlated with the gamma-glutamyltransferase level after KPE (0.05). Patients with early detectable had significantly lower total and direct bilirubin 3 months after KPE (0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable had reduced total and direct bilirubin after KPE.
The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of in early infancy correlating with better long-term outcomes.
() is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.
肠道微生物群在肝脏疾病中起重要作用，但其对胆道闭锁（BA）的具体影响仍有待探索。我们旨在研究BA患者早期的微生物特征，并分析其对长期预后的影响。
收集42例BA婴儿在Kasai肝门肠吻合术（KPE）前后的粪便样本。使用16S rRNA下一代测序分析粪便微生物群，并与年龄匹配的健康对照（HC）进行比较。采用鸟枪法宏基因组测序分析来确认KPE前10份粪便样本中的细菌组成。评估微生物特征与肝功能及长期预后的相关性。
在粪便微生物群的16S rRNA下一代测序分析中，α和β多样性分析显示HC与KPE前后的BA患者之间存在显著差异。通过线性判别分析和随机森林分类分析的微生物组成差异显示，KPE前后患者中（某细菌名称）的丰度显著低于HC。（某细菌名称）的丰度与KPE后γ-谷氨酰转移酶水平呈负相关（P<0.05）。早期可检测到（某细菌名称）的患者在KPE后3个月时总胆红素和直接胆红素显著较低（P<0.005），且肝移植率显著较低（风险比：0.16，95%CI 0.03 - 0.83，P = 0.029）。鸟枪法宏基因组测序还显示，有可检测到（某细菌名称）的BA患者在KPE后总胆红素和直接胆红素降低。
BA患者的肠道微生物群与HC不同，婴儿早期（某细菌名称）的丰度显著与更好的长期预后相关。
（某细菌名称）是人类肠道中常见的有益细菌。已对其对各种健康状况的潜在影响进行了研究。在胆道闭锁患者中，我们发现粪便微生物群中（某细菌名称）丰度更高与临床结局改善相关。这表明肠道中该细菌的早期定植和水平增加可能是改善胆道闭锁患者预后的一种治疗策略。
