Jain Vandana, Dalby Matthew J, Alexander Emma C, Burford Charlotte, Acford-Palmer Holly, Serghiou Iliana R, Teng Nancy M Y, Kiu Raymond, Gerasimidis Konstantinos, Zafeiropoulou Konstantina, Logan Michael, Verma Anita, Davenport Mark, Hall Lindsay J, Dhawan Anil
Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, UK.
Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
Hepatol Commun. 2024 Oct 17;8(11). doi: 10.1097/HC9.0000000000000550. eCollection 2024 Nov 1.
The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.
Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.
Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.
Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.
葛西肝门空肠吻合术（KPE）旨在重建胆道闭锁（BA）患者的胆汁流动；然而，BA仍然是儿科肝移植最常见的指征。肠道微生物群与宿主的相互作用越来越多地与慢性肝病的预后相关。本研究对BA患者的粪便微生物群和脂肪酸代谢产物进行了特征分析。
前瞻性收集新诊断的BA婴儿（n = 55）在KPE手术前后的粪便样本。收集年龄匹配的健康对照（n = 19）和胆汁淤积对照（n = 21）的粪便样本。进行粪便16S rRNA基因扩增子测序以分析肠道微生物群，并采用气相色谱法分析粪便脂肪酸。
与健康婴儿相比，KPE术前BA婴儿和胆汁淤积对照婴儿中肠球菌的丰度增加。在KPE术后早期时间点，BA组与健康队列相比，α多样性增加。BA婴儿中双歧杆菌的相对丰度较低，而肠球菌、梭菌、梭杆菌和假单胞菌的相对丰度增加。KPE术后早期BA婴儿的粪便乙酸盐减少，粪便丁酸盐和丙酸盐升高。KPE术后较高的α多样性与不良临床结局（6个月黄疸和肝移植）相关。KPE术后较高的链球菌和梭杆菌相对丰度以及较低的瘤胃球菌属、布劳特氏菌属和颤螺菌属相对丰度与不良临床结局相关。布劳特氏菌属与肝病严重程度呈负相关，双歧杆菌与纤维化生物标志物呈负相关。在KPE术后6个月内发生胆管炎的婴儿中，双歧杆菌丰度显著降低。
KPE术后早期微生物群多样性增加、致病菌富集和有益微生物群减少均是与BA不良预后相关的因素。术后早期对肠道微生物群的调控可能具有治疗潜力。
