Manipulation of Visceral Hypersensitivity With Probiotic Bacteria in Irritable Bowel Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Clinical symptoms
研究概览
简要总结
Irritable bowel syndrome is a common digestive disorder worldwide. However, there is no effective treatment of irritable bowel syndrome. Visceral pain thresholds in response to stress are lower in patients with IBS compared to healthy volunteers, but the triggers to visceral hypersensitivity remain largely unknown. Animal models suggest roles for both host immune response and intestinal bacteria in the induction of visceral hypersensitivity. For instance colorectal distension increased in association with an alteration in bacterial flora induced by antibiotic therapy, which suggest a relationship between bacterial gut content and visceral afferent processing. Intestinal bacteria play a significant role in inducing IBS. Clinical studies have shown that manipulation of the commensal microbiota with probiotic bacteria, in particularly preparations that contain bifidobacteria, can alleviate IBS symptoms. Serotonin (5-HT) plays a crucial role in the regulation of gastrointestinal physiology and alterations in mucosal serotonin signaling is a possible mechanism of altered function and sensation in patients with IBS. Impairment of serotonin reuptake transporter (SERT) expression and function may also play a role in IBS. The investigators hypothesise that bacteria modulate sensory afferent and serotonin signaling necessary for visceral sensation and that these pathways can be targeted for therapy of IBS using probiotic bacteria. The first part of this study will be a cross-sectional study comparing the colonic microbiota and SERT polymorphisms in IBS patients and healthy controls. The second part will be an open-label pilot study to assess the effects of oral probiotic bacteria in visceral hypersensitivity and mucosal microbiota in patients with IBS. Clinical response will be assessed based on IBS symptom score and rectal sensitivity, and changes in mucosa microbiota will be measured using 454 pyrosequencing. This proposal will provide novel data on gut microbiota in Asian IBS patients, and explore the mechanisms underlying visceral hypersensitivity to direct future targeting of therapy in IBS.
详细描述
Background
An incomplete understanding of the mechanisms underlying irritable bowel syndrome (IBS) has hampered the development of an effective therapy for this condition. This is long overdue for a condition that affects at least 20 percent of the population (1), and has a major impact on patient's quality of life (QOL) (2).Current understanding of the underlying aetiology and pathogenesis of IBS is centered on two levels: the brain-gut axis which provides concept of how stress, emotion and psychological conditions all alter the perception of IBS symptoms. Within the intestinal wall, the patho-physiological mechanisms that are implicated in IBS include infection, immune activation, dysmotility, abnormal fermentation and visceral hypersensitivity. Studies have shown that visceral pain thresholds in response to stress are lower in patients with IBS compared to healthy volunteers (3). This hypersensitivity is apparent in response to both a physical and chemical stimulus but the triggers to visceral hypersensitivity remain largely unknown. intestinal bacteria play a significant role in inducing IBS. For instance post-infectious IBS developed in a subgroup of patients following a bout of gastroenteritis (4). Manipulation of the commensal microbiota can alleviate IBS symptoms and there is some evidence that probiotic preparations containing certain Bifidobacteria may be particularly effective (5). This proposal will focus on further exploration of the mechanisms underlying visceral hypersensitivity to direct future targeting of therapy with probiotic preparation.
Aims The aims of this study are (i) to identify IBS-associated changes in intestinal microbiota; (ii) to study SERT expression and genotyping, and their relationship with the gut microbiota, and (iii) to determine whether probiotic therapy alters visceral sensitivity in IBS patients and whether probiotic-induced changes in visceral hypersensitivity are associated with changes in the intestinal microbiota.
Hypothesis The investigators postulate that bacteria modulate sensory afferent signalling and serotonin signalling, necessary for visceral sensation and that these pathways can be targeted for therapy of IBS using probiotic bacteria.
RESEARCH PLAN This study consists of two parts. The first part will be a cross-sectional study comparing the colonic microbiota and SERT expression in IBS patients and healthy controls. The second part will involve a pilot open-label study to assess the effects of oral probiotic bacteria in visceral hypersensitivity, SERT expression and mucosal microbiota in patients with IBS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Symptoms of abdominal pain or discomfort of at least 3 times a month, in the last 6 months, associated with 2 or more of the following:
- •Improvement with defecation
- •Onset associated with a change in frequency of stool
- •Onset associated with a change in form (appearance) of stool
排除标准
- •history of weight loss or rectal bleeding
- •history of psychiatric illness (severe depression, mania and schizophrenia)
- •history of active infection
- •recent antibiotic therapy or anti-inflammatory medication
结局指标
主要结局
Clinical symptoms
时间窗: 4 weeks post probiotic
次要结局
- Differences in gut microbiota between IBS patients and controls(1 year)
- Difference in gut microbiota post probiotic in IBS patients(1 year)
- Differences in blood and mucosal SERT polymorphisms between IBS patients and controls(1 year)
- Rectal sensitivity(4 weeks post probiotics)