Alcohol, bacterial dysbiosis, and inflammation during colitis

酒精、细菌失调和结肠炎期间的炎症

• 批准号: 10062464
• 负责人: Paulius Kuprys
• 金额: $ 5.1万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062464
• 关键词: 3-nitrotyrosine; Abdomen; Accounting; Affect; Agreement; Alcohol consumption; Alcohols; Antibiotics; Bacteria; Body Weight decreased; Colitis; Colon; Crohn' s disease; Databases; Decontamination; Disease; Enterobacteriaceae; Epithelial Cells; Ethanol; Etiology; Exhibits; Exposure to; Feces; Flare; Food; Goals; Growth; Guidelines; Harvest; Health Care Costs; Hemorrhagic colitis; Hospitalization; Immunohistochemistry; Individual; Infiltration; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intestines; Large Intestine; Lead; Length; Mediating; Metabolism; Modeling; Mucous Membrane; Mucous body substance; Mus; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Pathogenicity; Pathology; Pathway interactions; Patients; Penetration; Periodicity; Physicians; Population; Production; Reactive Oxygen Species; Recombinant DNA; Recurrent disease; Relapse; Research; Role; Severities; Sodium Dextran Sulfate; Symptoms; Tight Junctions; Tissues; Ulcer; Ulcerative Colitis; United States; Water; alcohol effect; alcohol exposure; aminoguanidine; associated symptom; base; dextran sulfate sodium induced colitis; dysbiosis; enteric infection; experience; experimental study; gastrointestinal symptom; immune function; inflammatory disease of the intestine; inhibitor/antagonist; intestinal epithelium; mouse model; nitrosative stress; prevent

Project Summary/Abstract The goal of this project is to better understand how the intestinal epithelial cells and bacterial populations can be altered by alcohol in the setting of intestinal inflammation. There are two main forms of inflammatory bowel disease: Crohn's disease (CD) and ulcerative colitis (UC). UC is an inflammatory disease of the large intestine with unknown etiology that affects more than three million individuals globally. These patients experience periodic episodes of disease reactivation characterized by severe abdominal discomfort and bloody diarrhea, often requiring hospitalization. Triggers of flares appear to be multifactorial but can be precipitated by certain foods. Current guidelines recommend for physicians to caution UC patients against drinking alcohol, yet only a few studies have examined the effects of alcohol in UC. One study found that patients with increased alcohol consumption had increased rates of UC disease relapse, while another found that alcohol consumption increased gastrointestinal symptoms associated with UC. Despite the implications of these studies, a mechanism for alcohol-mediated relapse in UC or exacerbation of gastrointestinal symptoms is not defined. Intestinal bacterial changes are common in UC patients and individuals with alcohol use. Altered intestinal bacterial populations that are persistent can lead to intestinal tissue damage and perpetuate a cycle of inflammation. In our lab, we developed a model to study UC and alcohol use. Mice are treated with dextran sulfate sodium (DSS), which recapitulates aspects of the UC disease, followed by a binge ethanol treatment. Mice that received the DSS and ethanol treatment had increases in intestinal tissue damage compared to mice that received DSS only. This was accompanied by alterations in bacterial populations, i.e., increased Enterobacteriaceae, that have been observed in UC. Furthermore, we identified increased expression of Nos2 which produces metabolites that can be used by Enterobacteriaceae. This led us to hypothesize that in the setting of DSS-induced colitis, alcohol promotes expression of Nos2 in the intestine, which provides substrates that allow for Enterobacteriaceae overgrowth. The increased Enterobacteriaceae exacerbates intestinal damage. In Aim 1 we will determine if increased Nos2 expression leads to increased Enterobacteriaceae after DSS and ethanol treatment. In Aim 2 we will determine if Nos2-mediated increase in Enterobacteriaceae results in increased intestinal pathology. Overall, this study will aid in our understanding of the inflammatory and bacterial changes that occur due to alcohol in UC.

项目摘要/摘要 该项目的目的是更好地了解肠上皮细胞和细菌种群如何 在肠道炎症的情况下通过酒精改变。炎症肠有两种主要形式 疾病：克罗恩病（CD）和溃疡性结肠炎（UC）。 UC是大肠的炎症性疾病 具有未知的病因，影响了全球超过300万个人。这些患者经历 以严重的腹部不适和血腥腹泻为特征的疾病重新激活的周期性发作， 通常需要住院。耀斑的触发器似乎是多因素的，但可以通过某些 食物。当前的指南建议医生警告UC患者不要喝酒，但只有 很少有研究检查酒精对UC的影响。一项研究发现酒精含量增加 消费量增加了UC疾病复发的发生率，而另一种发现酒精消耗量 与UC相关的胃肠道症状增加。尽管这些研究有影响，但 尚未定义酒精介导的UC介导的复发或加剧胃肠道症状的机制。 UC患者和饮酒患者常见肠道细菌的变化很常见。肠道改变 持续存在的细菌种群会导致肠道组织损害，并使 炎。在我们的实验室中，我们开发了一种研究UC和饮酒的模型。小鼠用葡聚糖治疗 硫酸钠（DSS），概括了UC疾病的各个方面，然后进行暴饮暴食。 与小鼠相比 仅收到DSS。伴随着细菌种群的改变，即增加 在UC中观察到的肠杆菌科。此外，我们确定了NOS2的表达增加 产生可以由肠杆菌科使用的代谢产物。这使我们假设 DSS诱导的结肠炎的设置，酒精促进NOS2在肠中的表达，该肠道提供了底物 这允许肠杆菌科过度生长。肠杆菌科的增加加剧了肠道 损害。在AIM 1中，我们将确定NOS2表达增加是否导致肠杆菌科的增加 DSS和乙醇处理。在AIM 2中，我们将确定NOS2介导的肠杆菌科的增加是否增加 导致肠道病理增加。总体而言，这项研究将有助于我们理解炎症 以及由于UC中的酒精而发生的细菌变化。

项目成果

Alcohol decreases intestinal ratio of Lactobacillus to Enterobacteriaceae and induces hepatic immune tolerance in a murine model of DSS-colitis.

• DOI: 10.1080/19490976.2020.1838236
• 发表时间: 2020-11-09
• 期刊: Gut microbes
• 影响因子: 12.2
• 作者: Kuprys PV;Cannon AR;Shieh J;Iftekhar N;Park SK;Eberhardt JM;Ding X;Choudhry MA
• 通讯作者: Choudhry MA

IL-22 and Lactobacillus delbrueckii mitigate alcohol-induced exacerbation of DSS-induced colitis.

• DOI: 10.1002/jlb.4a0122-068r
• 发表时间: 2022-12
• 期刊: JOURNAL OF LEUKOCYTE BIOLOGY
• 影响因子: 5.5
• 作者: Cannon, Abigail R.;Shim, Esther H.;Kuprys, Paulius, V;Choudhry, Mashkoor A.
• 通讯作者: Choudhry, Mashkoor A.