Satapathy Sanjaya K, Banerjee Pratik, Pierre Joseph F, Higgins Daleniece, Dutta Soma, Heda Rajiv, Khan Sabrina D, Mupparaju Vamsee K, Mas Valeria, Nair Satheesh, Eason James D, Kleiner David E, Maluf Daniel G
Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY.
Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN.
Transplant Direct. 2020 Nov 10;6(12):e625. doi: 10.1097/TXD.0000000000001033. eCollection 2020 Dec.
Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT.
Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018-December 2018). Genomic DNA extraction, next-generation sequencing, and quantitative PCR analysis were performed on stool samples collected within 1.1 ± 1.6 y from time of liver biopsy.
Recurrent NAFLD was noted in 15 of the 21 included patients. Stool microbiome analysis at the genus level showed significant loss of and increasing associated with NAFLD recurrence. Quantitative PCR analysis revealed significantly decreased relative abundance of Firmicutes in patients with NAFLD activity scores (NASs) ≥5 as compared with patients with lower NAS scores, whereas Bacteroidetes were significantly increased with higher NAS ( < 0.05). Firmicutes ( = 0.007) and group ( = 0.037) were inversely correlated, whereas Bacteroidetes ( = 0.001) showed a positive correlation with higher hepatic steatosis content. The Firmicutes/Bacteroidetes ratios were higher in patients without NAFLD or NASH as compared with patients diagnosed with NAFLD or NASH at the time of sample collection.
, Firmicutes, and may play protective roles in the development of recurrent NAFLD in LT recipients, whereas Fusobacteria and Bacteroidetes may play pathogenic roles. These findings highlight the potential role of the "gut-liver" axis in the pathogenesis of NAFLD recurrence after LT.
非酒精性脂肪性肝病（NAFLD）及其进展型非酒精性脂肪性肝炎（NASH）在全球范围内是一个日益严重的问题，即使在肝移植（LT）后也会复发。我们旨在描述LT后复发性NAFLD患者与未复发患者相比的肠道菌群失调情况。
前瞻性纳入21例因NASH接受LT且在LT后1年以上进行了方案肝活检的患者（2018年1月至2018年12月）。对肝活检后1.1±1.6年内收集的粪便样本进行基因组DNA提取、二代测序和定量PCR分析。
21例纳入患者中有15例出现复发性NAFLD。属水平的粪便微生物组分析显示，与NAFLD复发相关的[具体菌属1]显著减少，[具体菌属2]增加。定量PCR分析显示，与NAS评分较低的患者相比，NAFLD活动评分（NAS）≥5的患者中厚壁菌门的相对丰度显著降低，而拟杆菌门随着NAS升高而显著增加（P<0.05）。厚壁菌门（P=0.007）与[具体菌属3]组呈负相关，而拟杆菌门（P=0.001）与较高的肝脂肪变性含量呈正相关。与样本采集时诊断为NAFLD或NASH的患者相比，未患NAFLD或NASH的患者的厚壁菌门/拟杆菌门比值更高。
[具体菌属1]、厚壁菌门和[具体菌属3]可能在LT受者复发性NAFLD的发生中起保护作用，而梭杆菌属和拟杆菌门可能起致病作用。这些发现突出了“肠-肝”轴在LT后NAFLD复发发病机制中的潜在作用。
