The Effect of Probiotics on E. Coli Gastroenteritis

Study Overview
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Brief Summary
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Background: The incidence of gastrointestinal infections is very high. In European countries 10-25% of the population suffers from at least one foodborne infection per year. Probiotics may strengthen human resistance to gut infections as they may beneficially modulate the intestinal microbiota composition and activity, and the immune function upon intestinal infection. Aim: To study whether probiotics improve the resistance of humans to enterotoxigenic E. coli (ETEC). Study design: The PRETEC study is a parallel, double-blind, placebo-controled 4-weeks intervention with probiotics in healthy volunteers. In this study, the effect of probiotic intervention vs placebo on several infection markers in response to an ETEC challenge is investigated. Participants will be randomly assigned to the probiotic or placebo group (n=21 per group). Subjects will be instructed to maintain their habitual food intake, but to standardize their dietary calcium intake. After an adaptation period of 2 weeks, subjects will be orally infected with a live, but attenuated, ETEC vaccine (strain E1392-75-2A; collection NIZO food research; dose will be 10E10 CFU). This ETEC strain induces mild and short-lived infectious diarrhea symptoms. Before and after infection, a diary will be kept to write down all food and drinks consumption (2x2 days) to assess the habitual dietary intake. The diary will also be used for daily recording of bowel habits and frequency and severity of gastrointestinal complaints. Blood is sampled for immune response analyses and multiple faecal samples are collected to quantify several infection- and immune system markers, to determine probiotic excretion, and to verify dietary calcium intake. Study population: Healthy males of 20-55 yrs of age. Interventions: Probiotics (freeze-dried powder, dose 10E9 CFU twice daily) or placebo (carrier material powder of identical appearance). Primary outcomes: Total fecal ETEC excretion per day and severity of diarrhea (quantified by faecal output per day). Secondary outcomes: Serum immune response to ETEC, self-reported stool consistency scores and gastrointestinal complaints, relative faecal wet weight, sIgA and calprotectin in faeces, probiotic persistence and levels of opportunistic pathogens in the endogenous microbiota.

Detailed Description
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The timeframes for analysis of the primary and secondary outcomes is mentioned below in the Outcome Measures section.

Official Title
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The Effect of Probiotics on E. Coli Gastroenteritis

Conditions
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Gastroenteritis, Bacterial Infection, Diarrhea

Intervention / Treatment
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* Dietary Supplement: probiotics
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Male Age 20-55 yrs Willingness to replace habitual dairy product intake with the supplied low- calcium soy milk products Willingness to abstain from products with high amounts of prebiotic fibers and products with probiotics (except for the supplied one) Exclusion Criteria: Current or previous underlying disease of the GI tract lactose intolerance Use of antibiotics, norit, laxatives, cholestyramine, acid burn inhibitors, immune suppressiva, prebiotics, probiotics detectable serum antibodies against ETEC carriage of streptomycin-resistant E. coli in faeces (only relevant when culturing technique for ETEC will be applied instead of specific RT-PCR) vegetarians heavy alcohol use drug use

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: probiotics<br>Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks | Dietary Supplement: probiotics<br>* Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks<br>|
| Placebo Comparator: placebo<br>Carrier material powder of identical appearance | Dietary Supplement: placebo<br>* placebo consisting of carrier material powder of identical appearance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total daily faecal ETEC excretion with time |  | 1-2 days before ETEC infection and on days 1, 2, 3, 5 and 15 after ETEC infection | 
| Total daily faecal output with time |  | 1-2 days before ETEC infection and on days 1, 2, 3, 5, 15 after ETEC infection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel habits |  | Scored daily in a diary | 
| Frequency and severity of gastrointestinal symptoms |  | Scored daily by VAS scales in a diary | 
| Diarrhea severity | Determined as % faecal wet weight | 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection | 
| Opportunistic pathogens in faeces |  | At a single day just before ETEC infection and at a single time point in the first week after ETEC infection | 
| Faecal calprotectin |  | 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection | 
| Serum antibody response to CFA II |  | At screening (baseline) and at days 9 and 15 after ETEC infection | 
| Total faecal sIgA |  | 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infectious diarrhea, probiotics, prevention, dietary intervention, E. coli infection, intestinal infection, intestinal resistance