Table_1_Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity.DOCX

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）是一类复杂且高发的疾病，当前可供选择的药物治疗方案十分有限。AUD的临床前动物模型通常采用多种自愿饮酒实验范式，以重现该疾病的不同病程阶段，包括酗酒式饮酒与成瘾依赖。然而，小鼠的自愿饮酒行为个体差异显著，导致不同实验室间的实验结果难以重复。日益增多的研究证据表明，不同品牌的市售啮齿类饲料会对酒精摄入量产生显著影响。
本研究采用24小时间歇接触范式，探究了3种商业化且广泛使用的啮齿类饲料配方对C57BL/6J小鼠酒精摄入量与偏好的影响。本次测试的3种饲料分别为：来自Research Diets公司的LabDiet 5,001（LD5001）、LabDiet 5,053（LD5053），以及来自Envigo公司的Teklad 2019S（TL2019S）。
实验结果显示，相较于饲喂TL2019S的小鼠，饲喂LD5001与LD5053的小鼠酒精摄入量与偏好程度显著更高。本研究还发现，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与偏好行为。进一步的实验表明，小鼠对蔗糖、糖精与奎宁的偏好并未因饲料更换而发生变化，提示饲料并未影响其甜味与苦味味觉感知。此外，饲喂LD5001的小鼠相较于饲喂TL2019S的个体，其抗奎宁的酒精摄入量显著升高，这表明饲料可能会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、分别摄入清水与酒精的小鼠的肠道菌群进行了表征分析，发现细菌的α多样性与β多样性存在显著差异，这类差异可能通过肠脑轴信号传导对酒精摄入行为产生影响。