Wang Brian, Peters-Samuelson Brandilyn A, Luo Kai, Cordero Christina, Perreira Krista M, Pirzada Amber, Daviglus Martha L, Li Yang, Kaplan Robert C, Burk Robert D, Qi Qibin
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Psychology, University of Miami, Miami, FL 33124, USA.
Nutrients. 2025 Aug 18;17(16):2669. doi: 10.3390/nu17162669.
BACKGROUND/OBJECTIVE: Alcohol consumption has been linked to alterations in gut microbiota and insulin resistance. The alcohol dehydrogenase 1B (ADH1B) gene plays a crucial role in alcohol catabolism, where rs1229984 variant carriers (CT/TT) catabolize ethanol at an 80-fold faster rate than non-carriers (CC). This study investigates the relationships between ADH1B gene rs1229984 mutation, alcohol consumption, gut microbiota, and insulin resistance.
We performed cross-sectional analysis on fecal metagenomic sequencing data from diabetes-free participants in a longitudinal cohort of the Hispanic Community Health Study/Study of Latinos. We used Analysis of Composition of Microbiomes to identify gut microbial species associated with alcohol consumption in non-carriers ( = 1399) and carriers ( = 193). We constructed genotype-specific gut microbiome scores (GMSs) based on the identified species associated with alcohol consumption to examine how gut microbiota may influence the relationship between alcohol consumption and insulin resistance across genotypes. Insulin resistance was defined as Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) > 2.5.
Distinct microbial species associated with alcohol consumption were identified in non-carriers (54 species) and carriers (16 species). In non-carriers, the genotype-specific GMS modified the relationship between alcohol consumption and insulin resistance (P = 0.011). The odds ratios (OR) for insulin resistance with increasing alcohol consumption levels across low, moderate, and high tertiles of GMS were 0.75 (95%CI 0.58-0.96), 0.82 (0.67-1), and 1.13 (0.93-1.39), respectively. We identified that individual alcohol-related species, such as Prevotella copri, Ruminococcus callidus, and Erysipelatoclostridium ramosum, modified the relationship between alcohol consumption and insulin resistance in non-carriers.
This study suggests that the ADH1B gene rs1229984 mutation is associated with gut microbiota profiles altered by alcohol consumption. Our findings also suggest a potential role of gut microbiota in the protective association between alcohol consumption and insulin resistance in the variant non-carriers.
背景/目的：饮酒与肠道微生物群改变及胰岛素抵抗有关。乙醇脱氢酶1B（ADH1B）基因在酒精分解代谢中起关键作用，其中rs1229984变异携带者（CT/TT）分解乙醇的速度比非携带者（CC）快80倍。本研究调查ADH1B基因rs1229984突变、饮酒、肠道微生物群和胰岛素抵抗之间的关系。
我们对西班牙裔社区健康研究/拉丁裔研究纵向队列中无糖尿病参与者的粪便宏基因组测序数据进行了横断面分析。我们使用微生物群落组成分析来确定非携带者（n = 1399）和携带者（n = 193）中与饮酒相关的肠道微生物物种。我们基于与饮酒相关的已鉴定物种构建了基因型特异性肠道微生物群评分（GMS），以研究肠道微生物群如何影响不同基因型饮酒与胰岛素抵抗之间的关系。胰岛素抵抗定义为胰岛素抵抗稳态模型评估（HOMA-IR）>2.5。
在非携带者（54种）和携带者（16种）中鉴定出与饮酒相关的不同微生物物种。在非携带者中，基因型特异性GMS改变了饮酒与胰岛素抵抗之间的关系（P = 0.011）。在GMS的低、中、高三分位数中，随着饮酒水平增加，胰岛素抵抗的比值比（OR）分别为0.75（95%CI 0.58 - 0.96）、0.82（0.67 - 1）和1.13（0.93 - 1.39）。我们确定，个别与酒精相关的物种，如普氏粪杆菌、瘤胃球菌和多枝梭菌，改变了非携带者中饮酒与胰岛素抵抗之间的关系。
本研究表明，ADH1B基因rs1229984突变与饮酒改变的肠道微生物群谱有关。我们的研究结果还表明，肠道微生物群在rs1229984变异非携带者饮酒与胰岛素抵抗之间的保护关联中可能发挥潜在作用。
