The design of this study conforms to a randomized double-blind placebo-controlled cross-over design.

The objective of the study is to assess the effect of three probiotics (Lactobacillus plantarum WCFS1, Lactobacillus plantarum CIP104448, and Lactobacillus plantarum CIP104450) on intestinal epithelial permeability and the immune system, in at least 8 healthy subject.

The effect of the three different probiotics and a placebo will be assessed on every subject in random sequence.

Prior to the start of a 7-days supplementation period (one of the three probiotic supplements or placebo), blood samples will be obtained and small intestinal permeability will be assessed by measuring the urinary extraction ratios of ingested water-soluble, non-degradable test probes, with and without indomethacin challenge (to compromise the gut). After each supplementation period the gut will be stressed again by the indomethacin protocol, followed by measurement of small intestinal permeability, whereupon blood samples will be taken and duodenal tissue samples will be obtained by standard gastroduodenoscopy. Each supplementation period will start 1 month after finishing the pervious test episode, in randomized sequence.

The primary objective of this study is to assess the effects of Lactobacillus plantarum WCFS1, Lactobacillus plantarum CIP104448, and Lactobacillus plantarum CIP104450 on intestinal epithelial permeability. Secondary objectives are to assess the effects on immune modulation, gene expression of peripheral blood mononuclear cells, small intestine epithelial gene regulation and tight junction proteins modulation, infiltration of immune cells in intestinal mucosa and immune markers in blood plasma.

The investigators hypothesize that Lactobacillus plantarum WCFS1, Lactobacillus plantarum CIP104448, and Lactobacillus plantarum CIP104450 will, each separately, significantly affect the innate immune system and intestinal permeability in humans.

Inclusion Criteria:

• Based on medical history and previous self-admitted examination, no gastrointestinal complaints can be defined.
• Age between 18 and 65 years.
• BMI between 20 and 30 kg/m2.

Exclusion Criteria:

• History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol.
• Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing.
• Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study.
• Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator).
• Pregnancy, lactation.
• Excessive alcohol consumption (>20 alcoholic consumptions per week).
• Smoking.
• Blood donation within 3 months before or after the study period.
• Self-admitted HIV-positive state.
• Known hypersensitivity or history of allergic reactions towards intake of non-steroidal anti-inflammatory drugs (NSAIDs) or non- or low caloric sweeteners of any kind.
• History of any side effects towards intake of pro- or prebiotic supplements of any kind.