Human milk is a rich source of oligosaccharides. Acidic oligosaccharides, such as sialyllactose (SL), contain sialic acid (SA) residues. In human milk, approximately 73% of SA is bound to oligosaccharides, whereas only 3% is present in free form. Oligosaccharides are highly resistant to hydrolysis in the gastrointestinal tract. Only a small portion of the available oligosaccharides in breast milk is absorbed in the neonatal small intestine. SL and sialylated oligosaccharides are thought to have significant health benefits for the neonate, because of their roles in supporting resistance to pathogens, gut maturation, immune function, and cognitive development. The need for SA to allow proper development during the neonatal period is thought to exceed the endogenous synthesis. Therefore, these structures are important nutrients for the neonate. Based on the potential benefits, SL and sialylated oligosaccharides may be interesting components for application in infant nutrition. Once the hurdle of limited availability of these oligosaccharides has been overcome, their functionality can be explored in more detail, and supplementation of infant formula may become feasible.

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.

Background:We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin (which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid fermentation. Aims: To compare the effects of dietary inulin and FOS on resistance of rats to Salmonella enterica serovar Enteritidis and to determine whether calcium phosphate counteracts the effects of fermentation. Methods: Male Wistar rats (n = 8 per group) were fed a human ''Western style diet''. Diets with 60 g/kg cellulose (control), FOS, or inulin had either a low (30 mmol/kg) or high (100 mmol/kg) calcium concentration. After an adaptation period of two weeks, animals were orally infected with 2610 9 colony forming units of Salmonella enterica serovar Enteritidis. Colonisation of salmonella was determined by quantification of salmonella in caecal contents. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites in time.Results: Inulin and FOS decreased intestinal pH and increased faecal lactobacilli and enterobacteria. Moreover, both prebiotics increased the cytotoxicity of faecal water and faecal mucin excretion. Both prebiotics increased colonisation of salmonella in caecal contents and enhanced translocation of salmonella. Dietary calcium phosphate counteracted most of the adverse effects of inulin and FOS. Conclusions: Both inulin and FOS impair resistance to intestinal infections in rats. This impairment is partially prevented by dietary calcium phosphate. The results of the present study await verification in other controlled animal and human studies.

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(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.

Background and aims: It is frequently assumed that dietary non-digestible carbohydrates improve host resistance to intestinal infections by stimulating the protective gut microflora. However, compelling scientific evidence from in vivo infection studies is lacking. Therefore, we studied the effect of several nondigestible carbohydrates on the resistance of rats to Salmonella enteritidis infection. Methods: Rats (n = 8 per group) were fed ''humanised'' purified diets containing 4% lactulose, fructooligosaccharides (FOS), resistant starch, wheat fibre, or cellulose. After an adaptation period of 2 weeks the animals were orally infected with S enteritidis. Supplement induced changes in faecal biochemical and microbiological parameters were studied before infection. Colonisation of salmonella was determined by studying the faecal excretion of this pathogen and translocation by analysis of urinary nitric oxide metabolites over time and classical organ cultures. Intestinal mucosal myeloperoxidase activity was determined to quantify intestinal inflammation after infection. Results: Despite stimulation of intestinal lactobacilli and bifidobacteria and inhibition of salmonella colonisation, FOS and lactulose significantly enhanced translocation of this pathogen. These supplements also increased cytotoxicity of faecal water and faecal mucin excretion, which may reflect mucosal irritation. In addition, caecal and colonic, but not ileal, mucosal myeloperoxidase activity was increased in infected rats fed FOS and lactulose. In contrast, cellulose, wheat fibre, and resistant starch did not affect the resistance to salmonella. Conclusions: In contrast to most expectations, FOS and lactulose impair the resistance of rats to intestinal salmonella infection. Obviously, stimulation of the endogenous lactobacilli and bifidobacteria is no guarantee of improved host defence against intestinal infections.