Assessment of the Gut Microbiome in Diverticulitis and Diverticulosis
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- assessment of gut microbiome
研究概览
简要总结
Colonic diverticula are outpouchings of the large bowel, and they occur in up to 60% of people over 60 years of age. About 10-25% of patients with diverticula will have symptoms. These can range from acute diverticulitis, which can be a lethal infection to symptomatic diverticular disease, which involves inflammation of the bowel and altered bowel habits, decreasing patients' quality of life. We do not know which patients will develop acute diverticulitis or which patients will develop diverticula in their colon.
We believe that diverticulitis may be associated with, or even caused by, alterations in the bacteria that live in the colon, known as the gut microbiome. Until recently it was too expensive and too complex to examine the microbiome in detail. We propose to examine for the first time in detail the microbiome of patients with acute diverticulitis and asymptomatic diverticulosis.
Stool samples will be analysed for gut microbiome composition by 16S ribosomal RNA gene pyrosequencing. There is a part of the bacterial cell, the ribosome, which is the same in all bacteria (16S). Through PCR, polymerase chain reaction, and sequencing, we can separate out the different types of bacteria in a sample. We can then look at the different kinds of bacteria in each patient population, as well as how diverse the populations are within the groups, and compared to other groups.
We hope to be able to discriminate between the microbiome of patients with acute diverticulitis and asymptomatic diverticulosis. This study many change how diverticulitis and diverticulosis are conceptualized and treated. Alterations in the microbiome in these disease states may be able to be treated, preventing further disease.
详细描述
Diverticulosis affects 60% of people over 60 and roughly 10-25% of individuals will have symptoms, ranging from acute diverticulitis requiring emergent intervention to symptomatic diverticular disease with persistent lower abdominal pain and altered bowel habits. Up to 5% of patients with acute diverticulitis will die while hospitalized. In spite of the prevalence and severity of its manifestations, fundamental questions remain about the nature of diverticulitis and diverticulosis.
The human colon contains 100 trillion bacteria, including hundreds of species and 10 times as many genes as the human genome. While alterations in the microbiome have been implicated in disease states such as Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD), the microbiome has not been adequately described in relation to colonic diverticula. As King's College Hospital has the only known dedicated Diverticular Disease clinic, we have a uniquely large patient population in which to learn about this condition.
When colonic diverticula become inflamed or perforate, patients have diverticulitis. Inciting factors for episodes of acute diverticulitis are not well characterized, but include age, lifestyle factors and certain medications. Clinicians have no way to predict which patients will get diverticulitis, nor how severe its presentation will be. In some cases of pericolonic diverticulitis (known as Hinchey I), inflammation may resolve even without antibiotics, while in other cases, perforated diverticulitis will include feculent peritonitis (Hinchey IV) and require emergent colon resection. Diverticulitis may be caused by alterations in the microbiome, but this has not been sufficiently addressed.
The majority of patients with asymptomatic diverticulosis, that is, the presence of colonic diverticula in the absence of symptoms, will never experience an episode of diverticulitis. There has been, however, some limited evidence that the microbiome in diverticulosis is altered, and similar to that in acute diverticulitis. If that is so, then predicting which patients will develop acute diverticulitis will remain impossible. It will also mean that research which did not assess or control for the presence of diverticula in patient populations will need to be revisited.
Currently, clinicians have no basis to predict (1) which patients will develop severe acute diverticulitis requiring surgery or (2) which patients will develop acute diverticulitis which will resolve with antibiotics. We believe that further insights into the gut microbiome will allow for better diagnostics and treatments in the future.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Groups A and B. Patients with acute diverticulitis - patients presenting to A&E at King's College Hospital with new onset abdominal pain, with or without a known diagnosis of diverticulitis
- •Groups C and D. Patients with asymptomatic diverticulosis and normal controls
- •Patients being assessed through the 2ww Colorectal Cancer pathway with a chief complaint of fresh PR bleeding and no other 'red flag' symptoms, who are not overly anxious over their diagnosis as assessed by a physician outside the study team.
排除标准
- •Groups A and B. Patients with acute diverticulitis
- •Patients in extremis- e.g. systolic blood pressure less than 80 on arrival or pulse greater than 115
- •Patients who have received antibiotics in the three months prior to presentation.
- •Vulnerable patient populations
- •Groups C and D. Patients with asymptomatic diverticulosis and normal controls
- •Patients with high levels of pre-test anxiety, as determined by their assessing physician, outside the study team
- •Patients who received antibiotics for any reason in the 3 months prior to inclusion
- •Vulnerable patient populations
结局指标
主要结局
assessment of gut microbiome
时间窗: at time of enrollment
Patients will give stool specimen or rectal swab after enrolling in the study. Stool samples will undergo 16S rRNA pyrosequencing for microbiome analysis.
次要结局
未报告次要终点