Righetti Riccardo, Cinque Felice, Lebouché Bertrand, Ramos Ballesteros Luz, Routy Jean-Pierre, Klein Marina B, Szabo Jason, Cox Joseph, Falutz Julian, Haraoui Louis-Patrick, Costiniuk Cecilia T, De Pokomandy Alexandra, Pembroke Thomas, Constante Marco, Santos Manuela, Sebastiani Giada
Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Infection and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Int J Mol Sci. 2025 Aug 22;26(17):8165. doi: 10.3390/ijms26178165.
The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to severe forms, including metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, involves metabolic dysfunction, genetics, and gut dysbiosis. People with HIV (PWH) represent a high-risk group for MASLD, but the role of gut microbiota alterations in disease severity within this population remains poorly understood. We prospectively recruited PWH with MASLD, defined as the controlled attenuation parameter (CAP) ≥ 238 dB/m, and excluded those with viral hepatitis coinfection or alcohol abuse. Severe MASLD was defined as the presence of MASH (cytokeratin-18 ≥ 130.5 U/L) and/or significant liver fibrosis (liver stiffness ≥ 7.1 kPa). Stool samples were collected for 16S rRNA gene sequencing to characterize gut microbiota composition. Functional predictions were generated using PICRUSt. The differential abundance of bacterial taxa and predicted functions were analyzed using a generalized linear model with a negative binomial distribution. Among 34 PWH with MASLD, 18 (53%) met the criteria for severe MASLD. Microbiota profiling revealed significant differences in bacterial genera between the PWH with and without severe MASLD. Enrichment was observed in the group, , , , the group, and , while depletion was seen in , , , , the group, , , , , and the group. Predicted functional pathways related to fatty acid degradation, folate biosynthesis, and amino acids metabolism did not differ between groups. MASLD severity in PWH is associated with a distinct gut microbiota signature, though not with functional pathway alterations. Microbial profiling may complement existing non-invasive biomarkers for risk stratification in this high-risk population.
代谢功能障碍相关脂肪性肝病（MASLD）进展为严重形式，包括代谢功能障碍相关脂肪性肝炎（MASH）和肝纤维化，涉及代谢功能障碍、遗传学和肠道生态失调。艾滋病毒感染者（PWH）是MASLD的高危人群，但肠道微生物群改变在该人群疾病严重程度中的作用仍知之甚少。我们前瞻性招募了MASLD的PWH，定义为受控衰减参数（CAP）≥238 dB/m，并排除了合并病毒肝炎或酗酒者。严重MASLD定义为存在MASH（细胞角蛋白-18≥130.5 U/L）和/或显著肝纤维化（肝脏硬度≥7.1 kPa）。收集粪便样本进行16S rRNA基因测序，以表征肠道微生物群组成。使用PICRUSt进行功能预测。使用具有负二项分布的广义线性模型分析细菌分类群和预测功能的差异丰度。在34例患有MASLD的PWH中，18例（53%）符合严重MASLD的标准。微生物群分析显示，患有和未患有严重MASLD的PWH之间细菌属存在显著差异。在 组、 组、 组、 组、 组和 组中观察到富集，而在 组、 组、 组、 组、 组、 组、 组和 组中观察到消耗。与脂肪酸降解、叶酸生物合成和氨基酸代谢相关的预测功能途径在各组之间没有差异。PWH中MASLD的严重程度与独特的肠道微生物群特征相关，尽管与功能途径改变无关。微生物分析可能会补充现有的非侵入性生物标志物，用于该高危人群的风险分层。
