Is small intestinal bacterial overgrowth associated with functional dyspepsia?

描述(申请人提供)：功能性消化不良(FD)影响约15%的人口。虽然许多发现与这些患者有关，包括对营养饮料的耐受量减少，但这种情况的病理生理学和治疗仍不清楚。餐后腹胀是FD的主要症状，患者注意到餐后腹胀。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患者在乳果糖呼气试验(LBT)上有细菌气体排泄异常，提示小肠细菌过度生长(SIBO)。SIBO是本土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都发生，导致细菌气体的过度产生，导致腹胀和肿胀。在IBS的随机、安慰剂对照抗生素治疗中，SIBO的成功治疗显著改善了胃肠道症状(如腹胀)和肠外症状(如疲劳)。目的：探讨系统性肠梗阻(SIBO)、消化间期运动异常和超敏反应在FD中的患病率及其相互关系。我们还将通过随机抗生素治疗来确定SIBO与FD超敏反应的关系。研究设计：我们将在一组FD患者和健康对照组中比较呼吸测试、消化间期动力和超敏反应。一种不可吸收的肠靶向抗生素治疗将以随机、双盲、安慰剂对照的方式进行。方法：我们将招募上消化道内窥镜检查阴性、24小时pH试验阴性的符合FD纳入标准的患者和健康对照组。我们将比较SIBO治疗前后问卷记录的症状评分、LBT结果、小肠测压和营养饮料的耐受量。临床关系：FD一直是一种令人困惑和致残的疾病，影响着大约15%的人口。目前的治疗方法是针对减轻症状，但特点是疗效不佳。确定肠道细菌对FD的解释将导致针对SIBO的新的诊断和治疗方法的发展。这将代表着FD患者临床护理的重大进步。公共卫生相关性功能性消化不良在人群中的患病率高达15%，是一种常见但知之甚少的疾病，缺乏有效的治疗。腹胀是这些患者的主要主诉。在这项提案中，我们将检验这一假设，即过度细菌发酵可能在功能性消化不良的腹胀和其他消化不良症状中发挥作用。

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.