Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission

University of Zurich40 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Salmonella Infection Non-Typhoid

Interventions

Blood samplesOTHER

Blood samples will be collected and analyzed at different study time points

Stool samplesOTHER

Stool samples will be collected and analyzed at different study time points

Clinical informationOTHER

Clinical information will be collected at different study time points using questionnaires

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 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) Exclusion Criteria: * 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.

Locations (1)

Division of Gastroenterology, University Hospital Zurich

Zurich, Switzerland

RECRUITING

Outcomes

Primary Outcomes

Genomic mutations in non-typhoid Salmonella strains

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.

Time frame: 4 weeks after index stool culture

Secondary Outcomes

Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors

Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes

Time frame: 4 weeks after index stool culture

Identification of most frequently mutated surface antigenes of non-typhoid Salmonella

Identification of escape mechanisms of non-typhoid Salmonella (i.e. mutation of surface antigens) to avoid specific immune responses (i.e. antibodies) during acute infection and remission.

Time frame: 4 weeks after index stool culture

Gen Cluster Expression

Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.

Time frame: 2 weeks, 4 weeks and 6 months after index stool culture

Mutated non-typhoid Salmonella strains

Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.

Time frame: 4 weeks and 6 months after index stool culture

Microbiota changes

Composition (i.e. number of bacteria species identified) and relative diversity of the gut microbial community during acute non-typhoid Salmonella infection and remission. Findings will be compared to changes occurring in the microbiota of healthy individuals and individuals with acute, infectious diarrhea caused by microorganisms other than Salmonella.

Central Contacts

Benjamin Misselwitz, PD Dr.med.

CONTACT

+41 44 255 1111 benjamin.misselwitz@usz.ch

Data from ClinicalTrials.gov

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