Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Genomic mutations in non-typhoid Salmonella strains
研究概览
简要总结
Stool and blood samples from patients with a non-typhoid Salmonella infection will be collected during an observation period of six months and analyzed for changes in the microbiota diversity and composition, mutation rates in the Salmonella strains and the specific immune response evoked by the infection. Findings are compared to healthy individuals and individuals with acute, infectious diarrhea caused by other microorganisms.
详细描述
Infection processes of a non-typhoid Salmonella infection in humans are not well understood and so far, only little research has been conducted in this area. Findings from preclinical studies, using mouse models, attributed a fundamental role in infection control to the gut microbiota and the host immune system (antibody response). In mouse models a non-typhoid Salmonella infection provokes a pronounced antibody response and salmonella-inflicted gut inflammation alters the microbiota diversity and composition in the gut lumen. To date there is only scarce evidence on similar effects in humans.
During the study, longitudinal stool and blood samples will be collected from patients with a non-typhoid Salmonella infection at different study time points (2 weeks, 4 weeks and 6 months after positive Salmonella stool culture) and analyzed for changes in the microbiota, mutation rates in the Salmonella strains and the specific immune response evoked by the infection (e.g. anti-bodies). At each study time point clinical information will be investigated with a questionnaire to assess current symptoms, medication etc. Findings will be compared to healthy individuals and patients with acute, infectious diarrhea caused by other microorganisms than non-typhoid Salmonella.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General inclusion criteria:
- •Signed informed consent.
- •Ability to understand and follow study procedures and understand informed consent
- •Age 18-75 years.
- •Inclusion criteria for patients with non-typhoid Salmonella infection (n=20)
- •Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
- •Stool cultures positive for non-typhoid Salmonella ≤4 weeks before inclusion
- •Inclusion criteria for patients with acute, infectious diarrhea without non-typhoid Salmonella infection (n=10)
- •Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
- •Stool cultures negative for non-typhoid Salmonella infection within ≤ 4 weeks
- •Inclusion criteria for healthy volunteers (n=10)
- •No symptoms of acute or chronic diarrhea (2 bowel movements per week to 2 per day)
排除标准
- •Current use of antibiotics
- •Medication with immunosuppressants (e.g. corticoids, biological therapy).
- •Major medical/surgical/psychiatric condition requiring ongoing management. Minor well controlled conditions (i.e. medically controlled arterial hypertension, occupational asthma) may be present.
- •Major diagnosis known to chronically affect gut microbiota (e.g. inflammatory bowel disease, liver cirrhosis, colon carcinoma, systemic sclerosis).
- •Current diagnosis of a hematological disorder (e.g. severe anemia with hemoglobin <7 g/dl, leukemia) or any other absolute contraindication for blood donation.
- •Participation in other clinical study interfering with study procedures.
- •Inability to understand study procedures in order to provide inform consent.
- •Previous participation in the same study.
结局指标
主要结局
Genomic mutations in non-typhoid Salmonella strains
时间窗: 4 weeks after index stool culture
Analyze the evolution of non-typhoid Salmonella during acute infection and remission in humans. The primary variable of interest is the number of observed genomic mutations in non-typhoid Salmonella strains.
次要结局
- Antibody producing cells(2 weeks and 4 weeks after index stool culture)
- Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors(4 weeks after index stool culture)
- Mutated non-typhoid Salmonella strains(4 weeks and 6 months after index stool culture)
- Identification of most frequently mutated surface antigenes of non-typhoid Salmonella(4 weeks after index stool culture)
- Gen Cluster Expression(2 weeks, 4 weeks and 6 months after index stool culture)
- Antibody repertoire(2 weeks and 4 weeks after index stool culture)
- Microbiota changes(2 weeks, 4 weeks and 6 months after index stool culture)
- Development of irritable bowel syndrome(End of observational period (6 months))
- Antibody producing B-cell clones(4 weeks after index stool culture)
- Antigen- Antibody recognition(4 weeks and 6 months after index stool culture)