Is small intestinal bacterial overgrowth associated with functional dyspepsia?

描述（由申请人提供）：功能性消化不良（FD）影响约15%的人群。虽然许多发现与这些患者有关，包括对营养饮料的耐受性降低，但这种情况的病理生理学和治疗方法仍不清楚。餐后腹胀是FD的主要症状，患者以餐后腹胀为主。腹胀是肠易激综合征（IBS）的共同症状，IBS是另一种功能性肠道疾病，患病率约为15%。最近，我们发现高达84%的IBS患者在乳果糖呼吸试验（LBT）中有细菌气体排泄异常模式，提示小肠细菌过度生长（SIBO）。SIBO是本地肠道细菌菌群近端进入小肠的异常扩张。SIBO与肠道渗漏、细菌易位和免疫激活有关，代表了宿主-肠道细菌关系的转变。在这种情况下，细菌发酵在小肠和大肠中发生，导致细菌气体的过量产生，导致腹胀和膨胀。在一项随机、安慰剂对照的IBS抗生素治疗中，SIBO的成功治疗显著改善了胃肠症状（如腹胀）和肠外症状（如疲劳）。目的：我们将确定FD中SIBO、异常消化间期运动和超敏反应的患病率及其相关性。我们还将通过随机抗生素治疗确定SIBO与FD超敏反应之间的关系。研究设计：我们将比较FD患者和健康对照者的呼吸测试、消化间期运动和过敏反应。一种不可吸收的，针对小肠的抗生素治疗将以随机，双盲，安慰剂对照的方式进行。方法：我们将招募符合FD纳入标准的上消化道内镜检查阴性和24小时pH阴性的患者以及健康对照者。我们将比较SIBO治疗前后在问卷调查、LBT结果、小肠测压和营养饮料耐受性上记录的症状评分。临床关系：FD是一种令人困惑和致残的疾病，影响了约15%的人口。目前的治疗旨在减轻症状，但其特点是疗效差。确定FD的肠道细菌解释将导致针对SIBO的新型诊断和治疗方法的发展。这将代表FD患者临床护理的重大进步。功能性消化不良的患病率高达15%，是一种常见但缺乏有效治疗的疾病。腹胀是这些病人的主要主诉。在本提案中，我们将验证过度细菌发酵可能在腹胀和其他功能性消化不良症状中发挥作用的假设。

DESCRIPTION (provided by applicant): Functional dyspepsia (FD) affects ~15% of the population. While numerous findings have been associated with these patients including reduced volume of tolerance to nutritive drinks, the pathophysiology and treatment of this condition remain unclear. Postprandial bloating is a key symptom of FD with patients noting abdominal distension after meals. Bloating is a symptom shared with irritable bowel syndrome (IBS), another functional bowel disorder with a prevalence of ~15%. Recently, we have shown that up to 84% of patients with IBS have an abnormal pattern of bacterial gas excretion on lactulose breath test (LBT) to suggest small intestinal bacterial overgrowth (SIBO). SIBO is the abnormal expansion of the indigenous gut bacterial flora proximally into the small intestine. SIBO is associated with leaky gut, bacterial translocation and immune activation to represent a shift in host-gut bacterial relationship. In this setting, bacterial fermentation takes place in both the small and large intestine resulting in excessive production of bacterial gases leading to bloating and distension. In a randomized, placebo- controlled antibiotic treatment of IBS, successful treatment of SIBO results in a significant improvement of both gastrointestinal symptoms such as bloating and extraintestinal symptoms such as fatigue. Objective: We will determine the prevalence and association of SIBO, abnormal interdigestive motility, and hypersensitivity in FD. We will also determine the relationship between SIBO and hypersensitivity of FD using randomized antibiotic treatment. Research design: We will compare in a cohort of FD patients and healthy controls breath testing, interdigestive motility and hypersensitivity. A nonabsorbable, small-bowel targeting antibiotic treatment will be administered in a randomized, double, blind, placebo-controlled manner. Methodology: We will recruit patients with negative upper gastrointestinal endoscopy and negative 24h pH study who meet the inclusion criteria for FD along with healthy controls. We will compare symptom scores recorded on questionnaires, LBT results, small bowel manometry, and volume of tolerance of a nutritive drink before and after treatment of SIBO. Clinical relationships: FD has been a perplexing and disabling disorder affecting ~15% of population. Current treatment is directed at symptom reduction but is characterized by poor efficacy. The identification of a gut bacterial explanation for FD will lead to the development of novel diagnostic and treatment approaches targeting SIBO. This will represent a major advance in the clinical care of FD patients. Public Health Relevance Functional dyspepsia with a prevalence of up to ~15% of the population is a common but poorly understood disorder without effective treatment. Bloating is a key complaint of these patients. In this proposal, we will test the hypothesis that excessive bacterial fermentation may play a role in the bloating and other dyspeptic symptoms of functional dyspepsia.