Tashkent Yasmina, Choo Jocelyn M, Richard Alyson, Wang Zhengyi, Calzadilla-Bertot Luis, Vasil Egi, Miller Sophie, Taylor Steven L, Ivey Kerry L, Woodman Richard, Adler Brendan, Ayonrinde Oyekoya T, Olynyk John K, Beilin Lawrence J, Mori Trevor A, Wigg Alan J, Muller Kate R, Adams Leon A, Rogers Geraint B
Microbiome and Host Health Program, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
Liver Int. 2025 Mar;45(3):e70032. doi: 10.1111/liv.70032.
Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.
At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).
SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.
The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).
脂肪性肝病（SLD）是全球慢性肝病的主要病因。由于SLD的发病机制与肠道微生物群改变有关，我们旨在通过利用一组特征明确的社区居住年轻成年人队列，在SLD发展的早期识别与SLD相关的肠道微生物群特征。
在27岁时，对第二代莱恩研究的588名参与者进行了横断面评估。使用经过验证的磁共振成像（MRI）肝脏体积脂肪分数（VLFF）方程（HepaFat）对肝脂肪变性进行量化。在588名参与者中，488名（83%）被归类为“无SLD”（VLFF≤3.55%），76名（12.9%）患有“轻度至中度”SLD（VLFF：3.56%-13.4%），24名（4.10%）患有“重度”SLD（VLFF>13.4%）。粪便微生物群分析发现，与无SLD相比，重度SLD与较低微生物群α多样性（观察到的特征[p = 0.015]、皮洛均匀度[p = 0.001]和香农多样性[p = 0.002]）之间存在关联。无SLD与轻度至中度（p = 0.004）和重度SLD组（p = 0.001）的粪便微生物群组成存在显著差异。SLD组之间的微生物群离散度无显著差异。产生短链脂肪酸的细菌相对丰度降低，促炎细菌类群水平升高，均与重度SLD显著相关（q<0.05）。
年轻成年人中的SLD与肠道微生物多样性降低以及细菌类群消耗模式有关，这与其他慢性炎症性疾病一致。我们对SLD早期发展中肠道微生物群特征的描述为风险识别和降低提供了潜在基础。
莱恩研究已在澳大利亚新西兰临床试验注册中心注册（ACTRN12617001599369）。
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