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In contrast to most expectations, we showed previously that dietary fructooligosaccharides (FOS) stimulate intestinal colonization and translocation of invasive Salmonella enteritidis in rats. Even before infection, FOS increased the cytotoxicity of fecal water, mucin excretion, and intestinal permeability. In the present study, we tested whether FOS has these effects in humans. A double-blind, placebo-controlled, crossover study of 2 x 2 wk, with a washout period of 2 wk, was performed with 34 healthy men. Each day, subjects consumed lemonade containing either 20 g FOS or placebo and the intestinal permeability marker chromium EDTA (CrEDTA). On the last 2 d of each supplement period, subjects scored their gastrointestinal complaints on a visual analog scale and collected feces and urine for 24 h. Fecal lactic acid was measured using a colorimetric enzymatic kit. The cytotoxicity of fecal water was determined with an in vitro bioassay, fecal mucins were quantified fluorimetrically, and intestinal permeability was determined by measuring urinary CrEDTA excretion. In agreement with our animal studies, FOS fermentation increased fecal wet weight, bifidobacteria, lactobacilli, and lactic acid. Consumption of FOS increased flatulence and intestinal bloating. In addition, FOS consumption doubled fecal mucin excretion, indicating mucosal irritation. However, FOS did not affect the cytotoxicity of fecal water and intestinal permeability. The FOS-induced increase in mucin excretion in our human study suggests mucosal irritation in humans, but the overall effects are more moderate than those in rats. KEY WORDS: * fructooligosaccharides * humans * microflora * mucin * prebiotics

We showed previously that fructooligosaccharides (FOS) decrease the resistance to salmonella infection in rats. However, the mechanism responsible for this effect is unclear. Therefore, we examined whether dietary FOS affects intestinal permeability before and after infection with Salmonella enterica serovar Enteritidis. Male Wistar rats were fed restricted quantities of a purified diet that mimicked the composition of a Western human diet. The diet was supplemented with 60 g/kg cellulose (control) or 60 g/kg FOS and with 4 mmol/kg of the intestinal permeability marker chromium EDTA (CrEDTA) (n = 8 or 10). After an adaptation period of 2 wk, rats were orally infected with [10.sup.8] colony-forming units (cfu) of S. enteritidis. Mucin concentrations in intestinal contents and mucosa were measured fluorimetrically, as markers of mucosal irritation. Intestinal permeability was determined by measuring urinary CrEDTA excretion. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites with time. Before infection, FOS increased mucosal lactobacilli and enterobacteria in cecum and colon, but not in the ileum. However, FOS increased cytotoxicity of fecal water and intestinal permeability. Moreover, FOS increased fecal mucin excretion and mucin concentrations in cecal and colonic contents, and in cecal mucosa before infection. After infection, mucin excretion and intestinal permeability in the FOS groups increased even further in contrast to the control group. In addition, FOS increased translocation of salmonella to extraintestinal sites. Thus, FOS impairs the intestinal barrier in rats, as indicated by higher intestinal permeability. Whether these results can be extrapolated to humans requires further investigation. KEY WORDS: * infection * microflora * mucin * prebiotics * salmonella

Prebiotics, such as fructo-oligosaccharides (FOS), stimulate the protective gut microflora, resulting in an increased production of organic acids. This may result in increased luminal killing of acid-sensitive pathogens. However, host defense against invasive pathogens, like salmonella, also depends on the barrier function of the intestinal mucosa. Rapid fermentation of prebiotics leading to high concentrations of organic acids may impair the barrier function. Therefore, we determined the dose-dependent effect of dietary FOS on the resistance of rats to Salmonella enteritidis. Male Wistar rats were fed restricted quantities of a 'humanized' purified diet supplemented with 0, 3 or 6 g/100 g of FOS (n = 7 in the 6% FOS group and n = 8 in the other diet groups). After an adaptation period of 2 wk, rats were orally infected with 1.7 x [10.sup.10] colony-forming units of S. enteritidis. Supplement-induced changes in the intestinal microflora and fecal cation excretion were determined before and after infection. Cytotoxicity of fecal water was determined with an in vitro bioassay, and fecal mucins were quantified fluorimetrically. Colonization of S. enteritidis was determined by quantification of salmonella in cecal contents and mucosa. Translocation of S. enteritidis was quantified by analysis of urinary nitric oxide metabolites in time. Before infection, FOS decreased cecal and fecal pH, increased fecal lactic acid concentration and increased bifidobacteria and enterobacteria. FOS also increased cytotoxicity of fecal water and fecal mucin excretion, indicating mucosal irritation. Remarkably, FOS dose-dependently increased salmonella numbers in cecal contents and mucosa and caused a major increase in infection-induced diarrhea. In addition, FOS enhanced translocation of salmonella. Thus, in contrast to most expectations, FOS dose-dependently impairs the resistance to salmonella infection in rats. These results await verification by other controlled animal and human studies. KEY WORDS: * fermentation * fructo-oligosaccharides * infection * prebiotics * rats * salmonella