Institute of Medical Pathology and Semeiotics , Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Institute of Microbiology , Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Alcohol Clin Exp Res. 2018 Dec;42(12):2313-2325. doi: 10.1111/acer.13900. Epub 2018 Oct 29.
There is strong evidence that alcoholism leads to dysbiosis in both humans and animals. However, it is unclear how changes in the intestinal microbiota (IM) relate to ethanol (EtOH)-induced disruption of gut-liver homeostasis. We investigated this issue using selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive EtOH consumption.
Independent groups of male adult sP rats were exposed to the standard, home-cage 2-bottle "EtOH (10% v/v) versus water" choice regimen with unlimited access for 24 h/d (Group Et) for 3 (T1), 6 (T2), and 12 (T3) consecutive months. Control groups (Group Ct) were composed of matched-age EtOH-naïve sP rats. We obtained samples from each rat at the end of each experimental time, and we used blood and colon tissues for intestinal barrier integrity and/or liver pathology assessments and used stool samples for IM analysis with 16S ribosomal RNA gene sequencing.
Rats in Group Et developed hepatic steatosis and elevated serum transaminases and endotoxin/lipopolysaccharide (LPS) levels but no other liver pathological changes (i.e., necrosis/inflammation) or systemic inflammation. While we did not find any apparent alteration of the intestinal colonic mucosa, we found that rats in Group Et exhibited significant changes in IM composition compared to the rats in Group Ct. These changes were sustained throughout T1, T2, and T3. In particular, Ruminococcus, Coprococcus, and Streptococcus were the differentially abundant microbial genera at T3. The KEGG Ortholog profile revealed that IM functional modules, such as biosynthesis, transport, and export of LPS, were also enriched in Group Et rats at T3.
We showed that chronic, voluntary EtOH consumption induced liver injury and endotoxemia together with dysbiotic changes in sP rats. This work sets the stage for improving our knowledge of the prevention and treatment of EtOH-related diseases.
有强有力的证据表明，酗酒会导致人类和动物的肠道菌群失调。然而，肠道微生物群（IM）的变化如何与乙醇（EtOH）引起的肠道-肝脏稳态破坏有关尚不清楚。我们使用经过选择性繁殖的撒丁岛酗酒倾向（sP）大鼠（一种过量摄入 EtOH 的验证动物模型）来研究这个问题。
将独立组的雄性成年 sP 大鼠暴露于标准的、家庭笼中的 2 瓶“EtOH（10%v/v）与水”选择方案中，每天 24 小时自由摄入（T1、T2 和 T3 组），连续 3、6 和 12 个月。对照组（Ct 组）由同龄的 EtOH 未接触的 sP 大鼠组成。在每个实验结束时，我们从每组大鼠中获得样本，并使用血液和结肠组织评估肠道屏障完整性和/或肝脏病理，使用粪便样本进行 16S 核糖体 RNA 基因测序分析肠道微生物群。
T1、T2 和 T3 时，T1、T2 和 T3 时，Et 组大鼠发生肝脂肪变性和血清转氨酶和内毒素/脂多糖（LPS）水平升高，但无其他肝脏病理变化（即坏死/炎症）或全身炎症。虽然我们没有发现肠道结肠黏膜有任何明显的改变，但我们发现 Et 组大鼠的肠道微生物群组成发生了显著变化，与 Ct 组大鼠相比。这些变化在 T1、T2 和 T3 时持续存在。特别是，在 T3 时，Ruminococcus、Coprococcus 和 Streptococcus 是差异丰度较高的微生物属。KEGG Ortholog 谱显示，在 T3 时，Et 组大鼠的肠道微生物群功能模块，如 LPS 的生物合成、转运和输出，也得到了富集。
我们表明，慢性、自愿性 EtOH 消耗导致了 sP 大鼠的肝损伤和内毒素血症，以及共生失调的变化。这项工作为提高我们对 EtOH 相关疾病的预防和治疗的认识奠定了基础。
Zotero 插件