Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Liver Int. 2024 May;44(5):1176-1188. doi: 10.1111/liv.15864. Epub 2024 Feb 14.
Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients.
113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4.
We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV.
In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.
细菌种类和微生物途径以及代谢物和临床参数可能相互作用，导致非酒精性脂肪性肝病（NAFLD）及其严重程度。我们使用集成机器学习模型和交叉验证方法来评估肥胖患者中的这种相互作用。
113 名接受减肥手术的患者具有临床和生化参数、血液和粪便代谢物测量以及粪便 shotgun 宏基因组测序，以分析肠道微生物组。肝脏组织学分类为正常肝脏肥胖（NLO；n=30）、单纯性脂肪变性（SS；n=41）或非酒精性脂肪性肝炎（NASH；n=42）；纤维化分级为 F0 至 F4。
我们发现，与 NLO 相比，NASH 患者中潜在有害的大肠杆菌增加，有益的 Alistipes putredinis 减少，ALT 和 AST 增加。血清葡萄糖、粪便 3-(3-羟苯基）-3-羟基丙酸和粪便胆酸升高，血清甘油磷脂降低。在 NAFLD 中，纤维化严重（F3-F4）与 F0 相比，抗炎物种（Eubacterium ventriosum、Alistipes finegoldii 和 Bacteroides dorei）丰度较低，AST、血清葡萄糖、粪便酰基辅酶 A、血清异亮氨酸和同型半胱氨酸升高，血清甘油磷脂降低。与 NLO 相比，NASH 患者中涉及氨基酸生物合成和降解的途径明显更为丰富，严重纤维化与menaquinol-10 生物合成超级途径和肽聚糖生物合成 IV 具有更强的整体显著关联。
在肥胖患者中，NASH 和严重纤维化与特定细菌种类、代谢途径和代谢物相关，这些可能导致 NAFLD 发病机制和疾病严重程度。
