Data_Sheet_1_Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity.PDF

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 h intermittent access procedure. The three brands of chow tested were LabDiet 5,001 (LD5001), LabDiet 5,053 (LD5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo, respectively). Mice fed LD5001 and LD5053 displayed higher levels of alcohol consumption and preference compared to mice fed TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48 h prior to alcohol administration. Sucrose, saccharin, and quinine preferences were not altered, suggesting that the diets did not alter sweet and bitter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of compulsive behaviors such as alcohol consumption. We profiled the gut microbiome of water- and alcohol-drinking mice that were maintained on different diets and found significant differences in bacterial alpha- and beta-diversities, which could impact the gut–brain axis signaling and alcohol consumption.

酒精使用障碍（Alcohol use disorder, AUD）是一种复杂且高发的疾病，目前可及的药物治疗手段十分有限。酒精使用障碍的临床前动物模型常采用多种自愿饮酒操作，以复现该疾病的不同病程阶段，包括暴饮式饮酒与酒精依赖。然而，小鼠的自愿饮酒行为个体差异极大，导致不同实验室间的实验结果难以重复。越来越多的研究证据表明，市售不同品牌的啮齿类动物饲料会对酒精摄入量产生显著影响。本研究采用24小时间断接触范式，探究了三种市售且广泛使用的啮齿类饲料配方对C57BL/6J小鼠酒精摄入量与酒精偏好的影响。本次测试的三种饲料分别为来自两家公司（分别为Research Diets与Envigo）的LabDiet 5001（LD5001）、LabDiet 5053（LD5053）以及Teklad 2019S（TL2019S）。与饲喂TL2019S的小鼠相比，饲喂LD5001与LD5053的小鼠表现出更高的酒精摄入量与酒精偏好。本研究同时发现，在酒精给药前48小时更换饲料，可快速改变小鼠的酒精摄入量与偏好。蔗糖、糖精与奎宁偏好未发生显著变化，表明饲料并未改变小鼠的甜、苦味觉感知能力。此外，与饲喂TL2019S的小鼠相比，饲喂LD5001的小鼠表现出更强的奎宁抵抗性饮酒行为，这提示饲料可影响强迫性饮酒等行为的发生发展。本研究对饲喂不同饲料的饮水与饮酒小鼠的肠道微生物组进行了表征分析，发现细菌的α多样性与β多样性存在显著差异，这些差异可能会影响肠-脑轴信号传导与酒精摄入量。