Prebiotic supplements and high-protein (HP) diets reduce body weight and modulate intestinal microbiota. Our aim was to elucidate the combined effect of an inulin/oligofructose (FOS) and HP diet on body weight gain, energy metabolism and faecal microbiota. Forty male C57BL/6NCrl mice were fed a control (C) diet for 2 weeks and allocated to a C or HP (40 % protein) diet including no or 10 % inulin/FOS (C + I and HP + I) for 4 weeks. Inulin/FOS was added in place of starch and cellulose. Body weight, food intake, faecal energy and nitrogen were determined. Indirect calorimetry and faecal microbiota analysis were performed after 3 weeks on diets. Body weight gain of HP-fed mice was 36 % lower than HP + I- and C-fed mice (P < 0⋅05). Diet digestibility and food conversion efficiency were higher in HP + I- than HP-fed mice (P < 0⋅01), while food intake was comparable between groups. Total energy expenditure (heat production) was 25 % lower in HP + I- than in C-, HP- and C + I-fed mice (P < 0⋅001). Carbohydrate oxidation tended to be 24 % higher in HP- than in HP + I-fed mice (P < 0⋅05). Faecal nitrogen excretion was 31–45 % lower in C-, C + I- and HP + I- than in HP-fed mice (P < 0⋅05). Faecal Bacteroides–Prevotella DNA was 2⋅3-fold higher in C + I- and HP + I- relative to C-fed mice (P < 0⋅05), but Clostridium leptum DNA abundances was 79 % lower in HP + I- than in HP-fed mice (P < 0⋅05). We suggest that the higher conversion efficiency of dietary energy of HP + I but not C + I-fed mice is caused by higher digestibility and lower heat production, resulting in increased body mass.

Breast milk composition varies with maternal factors including diet and confers health benefits to the neonate; however, the mechanisms mediating this protection remain incompletely understood. Our aim was to investigate the effects of supplementing a maternal high-fat/sucrose (HFS) diet with prebiotic oligofructose (OFS) on milk composition in rats and associations with offspring body composition and gut microbiota. Obese Sprague–Dawley dams consumed a control, HFS, HFS + OFS (10 % wt/wt) or HFS diet weight-matched to the HFS + OFS group (HFS-WM) during pregnancy and lactation. Pups were weaned onto a HFS diet on day 21. Milk was collected at weaning and analysed for protein, leptin and microRNA (miRNA) levels. Milk produced by HFS dams contained less protein than milk from lean controls which was normalised by OFS. Six miRNA (miR-222, miR-203a, miR-200a, miR-26a, miR-27a and miR-103) were differentially expressed in milk according to maternal diet. Milk leptin content was positively correlated with maternal body fat and faecal Enterobacteriaceae in male offspring at 24 weeks of age. Milk protein content was inversely associated with maternal body fat and body weight. miR-200a was positively associated with maternal body fat and Enterobacteriaceae in female offspring at 24 weeks of age. Correlations between milk protein and multiple milk miRNA and offspring body composition and gut microbiota differed by sex. Overall, our results suggest that obesogenic diets and prebiotic supplementation can alter the protein and miRNA levels in breast milk in rats and these milk components may explain, in part, the influence of these maternal diets on offspring body composition.

Oligofructose is a prebiotic dietary fibre obtained from chicory root inulin. Oligofructose supplementation may affect satiety, food intake, body weight and/or body composition. The aim was to examine the efficacy of oligofructose-supplemented granola bars on the following weight management outcomes: satiety, energy intake, body weight and body composition in overweight or obese adults. In all, fifty-five adults with overweight or obesity (thirty-six females/nineteen males; age: 41 (sd 12) years; 90·6 (sd 11·8) kg; BMI: 29·4 (sd 2·6) kg/m2) participated in a parallel, triple-blind, placebo-controlled intervention. A total of twenty-nine subjects replaced their snacks twice a day with an equienergetic granola bar supplemented with 8 g of oligofructose (OF-Bar). Subjects in the control group (n 26) replaced their snack with a control granola bar without added oligofructose (Co-Bar). Satiety, 24-h energy intake, body weight and body composition (fat mass and waist circumference) were measured at baseline, weeks 6 and 12. In addition, weekly appetite and gastrointestinal side effects were measured. During the intervention, energy intake, body weight and fat mass remained similar in the Co-Bar and OF-Bar groups (all P>0·05). Both groups lost 0·3 (sd 1·2) kg lean mass (P<0·01) and reduced their waist circumference with −2·2 (sd 3·6) cm (P<0·0001) after 12 weeks. The OF-Bar group reported decreased hunger in later weeks of the intervention (P=0·04), less prospective food consumption (P=0·03) and less thirst (P=0·003). To conclude, replacing daily snacks for 12 weeks with oligofructose-supplemented granola bars does not differentially affect energy intake, body weight and body composition compared with a control bar. However, there was an indication that appetite was lower after oligofructose bar consumption.

Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake.

Wheat bran extract (WBE) is a food-grade soluble fibre preparation that is highly enriched in arabinoxylan–oligosaccharides. In this placebo-controlled cross-over human intervention trial, tolerance to WBE as well as the effects of WBE on faecal parameters, including faecal output and bowel habits, were studied. After a 2-week run-in period, twenty healthy volunteers consumed WBE (15 g/d in the first week, 30 g/d in the second week), oligofructose (15 g/d in the first week, 30 g/d in the second week) and placebo (for 2 weeks) in a random order, with 2-week washout periods between each treatment period. Subjects collected a 72 h stool sample for analysis of faecal output, stool pH and stool moisture concentration. Additionally, the volunteers completed questionnaires scoring occurrence frequency and distress severity of eighteen gastrointestinal (GI) symptoms. An overall GI symptom measure was calculated to analyse the overall effect of WBE and oligofructose on GI symptoms. Intake of both 30 g/d WBE and 30 g/d oligofructose lowered stool pH, indicative of increased colonic fermentation, and increased stool moisture concentration as compared with placebo intake. Intake of 30 g/d oligofructose increased the overall GI symptom measure by 1·9-fold as compared with placebo intake. Intake of WBE at doses up to 30 g/d did not affect the overall GI symptom measure. WBE exerts beneficial effects on stool characteristics and is well tolerated at up to 30 g/d. Oligofructose exerts comparable beneficial effects on stool characteristics. However, intake of 30 g/d oligofructose appears to cause GI discomfort to some extent.

The impact of oligofructose (OF) intake on stool frequency has not been clearly substantiated, while significant gastrointestinal (GI) symptoms have been reported in some individuals. The aim of the present study was to determine the effects of OF on stool frequency and GI symptoms in healthy adults. In an 8-week, randomised, double-blind, parallel-arm study, ninety-eight participants were provided with 16 g OF in yogurt and snack bars (twenty male and thirty female) or matching control foods (seventeen male and thirty-one female), to incorporate, by replacement, into their usual diets. Participants completed a daily online questionnaire recording stool frequency and rating four symptoms: bloating, flatulence, abdominal cramping and noise, each on a Likert scale from ‘0’ for none (no symptoms) to ‘6’ for very severe, with a maximum symptom intensity score of 24 (sum of severities from all four symptoms). Online 24 h dietary recalls were completed during pre-baseline and weeks 4, 6 and 8 to determine fibre intake. When provided with OF foods, fibre intake increased to 24·3 (sem 0·5) g/d from pre-baseline (12·1 (sem 0·5) g/d; P < 0·001). Stool frequency increased with OF from 1·3 (sem 0·2) to 1·8 (sem 0·2) stools per d in males and 1·0 (sem 0·1) to 1·4 (sem 0·1) stools per d in females during intervention weeks compared with pre-baseline (P < 0·05),but did not change for control participants (males: 1·6 (sem 0·2) to 1·8 (sem 0·2); females: 1·3 (sem 0·1) to 1·4 (sem 0·1)). Flatulence was the most commonly reported symptom. Mean GI symptom intensity score was higher for the OF group (3·2 (sem 0·3)) v. control (1·7 (sem 0·1)) (P < 0·01), with few participants reporting above moderate symptoms. No change in symptom intensity occurred over time. Consuming yogurt and snack bars with 16 g OF improves regularity in young healthy adults. However, GI symptoms, resulting from an increase in oligofructose intake, may not diminish with time.

There is a growing interest in modulating gut microbiota with diet in the context of obesity. The purpose of the present study was to evaluate the dose-dependent effects of prebiotics (inulin and oligofructose) on gut satiety hormones, energy expenditure, gastric emptying and gut microbiota. Male lean and obese JCR:LA-cp rats were randomised to either of the following: lean 0 % fibre (LC), lean 10 % fibre (LF), lean 20 % fibre (LHF), obese 0 % fibre (OC), obese 10 % fibre (OF) or obese 20 % fibre (OHF). Body composition, gastric emptying, energy expenditure, plasma satiety hormone concentrations and gut microbiota (using quantitative PCR) were measured. Caecal proglucagon and peptide YY mRNA levels were up-regulated 2-fold in the LF, OF and OHF groups and 3-fold in the LHF group. Ghrelin O-acyltransferase mRNA levels were higher in obese v. lean rats and decreased in the OHF group. Plasma ghrelin response was attenuated in the LHF group. Microbial species measured in the Bacteroidetes division decreased, whereas those in the Firmicutes increased in obese v. lean rats and improved with prebiotic intake. Bifidobacterium and Lactobacillus increased in the OHF v. OC group. Bacteroides and total bacteria negatively correlated with percentage of body fat and body weight. Enterobacteriaceae increased in conjunction with glucose area under the curve (AUC) and glucagon-like peptide-1 AUC. Bacteroides and total bacteria correlated positively with ghrelin AUC yet negatively with insulin AUC and energy intake (P < 0·05). Several of the mechanisms through which prebiotics act (food intake, satiety hormones and alterations in gut microbiota) are regulated in a dose-dependent manner. The combined effects of prebiotics may have therapeutic potential for obesity.

The recently discovered SCFA-activated G-coupled protein receptors FFA receptor 2 and FFA receptor 3 are co-localised in l-cells with the anorexigenic ‘ileal brake’ gut hormone peptide YY, and also in adipocytes, with activation stimulating leptin release. Thus, SCFA such as acetate and propionate show promise as a candidate to increase satiety-enhancing properties of food. We therefore postulate SCFA may have a role in appetite regulation and energy homeostasis. SCFA can be delivered either directly within food, or indirectly via the colon by the provision of fermentable non-digestible carbohydrates. A review of studies investigating the effects of oral SCFA ingestion on appetite suggests that while oral SCFA ingestion is associated with enhanced satiety, this may be explained by product palatability rather than a physiological effect of SCFA. Colon-derived SCFA generated during microfloral fermentation have also been suggested to explain satiety-enhancing properties of non-digestible carbohydrates. However, findings are mixed from investigations into the effects of the prebiotic inulin-type fructans on appetite. Overall, data presented in this review do not support a role for SCFA in appetite regulation.

β2-1 Fructans are carbohydrate molecules with prebiotic properties. Through resistance to digestion in the upper gastrointestinal tract, they reach the colon intact, where they selectively stimulate the growth and/or activity of beneficial members of the gut microbiota. Through this modification of the intestinal microbiota, and by additional mechanisms, β2-1 fructans may have beneficial effects upon immune function, ability to combat infection, and inflammatory processes and conditions. In this paper, we have collated, summarised and evaluated studies investigating these areas. Twenty-one studies in laboratory animals suggest that some aspects of innate and adaptive immunity of the gut and the systemic immune systems are modified by β2-1 fructans. In man, two studies in children and nine studies in adults indicate that the adaptive immune system may be modified by β2-1 fructans. Thirteen studies in animal models of intestinal infections conclude a beneficial effect of β2-1 fructans. Ten trials involving infants and children have mostly reported benefits on infectious outcomes; in fifteen adult trials, little effect was generally seen, although in specific situations, certain β2-1 fructans may be beneficial. Ten studies in animal models show benefit of β2-1 fructans with regard to intestinal inflammation. Human studies report some benefits regarding inflammatory bowel disease (four positive studies) and atopic dermatitis (one positive study), but findings in irritable bowel syndrome are inconsistent. Therefore, overall the results indicate that β2-1 fructans are able to modulate some aspects of immune function, to improve the host's ability to respond successfully to certain intestinal infections, and to modify some inflammatory conditions.

In genetically susceptible individuals, an altered mucosal immune response against some commensal bacteria of the gut ecosystem appears to be the principal mechanism leading to intestinal lesions in inflammatory bowel disease (IBD). The information currently available does not provide an exact explanation about the origin of this important dysfunction of the interaction between host and commensal bacteria, but an altered microbial composition has been detected in the gut ecosystem of patients with Crohn's disease or ulcerative colitis. Prebiotics are food ingredients not digested nor absorbed in the upper intestinal tract that are fermented by intestinal bacteria in a selective way promoting changes in the gut ecosystem. Experimental and human studies have shown that inulin and oligofructose stimulate saccharolysis in the colonic lumen and favour the growth of indigenous lactobacilli and bifidobacteria. These effects are associated with reduced mucosal inflammation in animal models of IBD. Strong experimental evidence supports the hypothesis that inulin and oligofructose can offer an opportunity to prevent or mitigate intestinal inflammatory lesions in human Crohn's disease, ulcerative colitis, and pouchitis. Encouraging results have been obtained in preliminary clinical trials.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72·2 (sd 6·4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0·05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0·05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0·05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0·887 ± 0·102 v. 1·104 ± 0·121 g/cm2; P < 0·01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

Health and wellbeing are challenged constantly by pathogens. A number of defence mechanisms exist to protect the body from pathogen colonisation and invasion, with an important role to play for the natural intestinal bacterial flora (mainly by bifidobacteria and lactobacilli). The present paper reviews the evidence on the effects of inulin and oligofructose on colonisation and translocation of pathogens and the prevention of intestinal diseases. In vitro experiments have shown that lactic acid-producing bacteria have antagonistic (antibacterial) activity against pathogens partly because of the production of organic acids which are the endproducts of inulin and oligofructose fermentation. In addition, studies with epithelial layers have shown that inulin and oligofructose inhibit pathogen colonisation and that endproducts of their fermentation have the ability to support barrier function. Furthermore, studies in various animal models have shown that inulin and oligofructose accelerate the recovery of beneficial bacteria, slow down pathogen growth, decreasing pathogen colonisation and systemic translocation. Finally, data from human intervention trials either in patients with intestinal disorders or disease, or prone to critical illness, found that inulin and oligofructose restore the balance when the gut microbial community is altered, inhibit the progression of disease or prevent it from relapsing and/or developing. To conclude, the dietary use of inulin and oligofructose offers a promising approach to restore microbial communities and to support barrier function of the epithelia by their prebiotic action. This may offer the host protection against invasion and translocation of pathogens (endogenous and/or exogenous) and in the prevention of gastrointestinal diseases.

Effects of different inulin-type fructan fractions were studied on atherosclerotic plaque formation in male apo E-deficient mice. Thirty-two mice were randomly divided into four groups and received either a semi-purified sucrose-based diet (control group), or diets in which sucrose was replaced in part by various inulin-type fructans (10 g/100 g): long-chain inulin, oligofructose, or an oligofructose-enriched inulin for 16 weeks. The presence of atherosclerotic plaques was assessed by histomorphometry in the aortic sinus. The apo E-deficient mice fed long-chain inulin or an oligofructose-enriched inulin had about 35 % and 25 % less atherosclerotic lesion area compared with the control group, respectively. Feeding long-chain inulin significantly reduced plasma cholesterol concentrations (P<0·001), and the three inulin-type fructans reduced triacylglycerol (TAG) concentrations compared with the control group (P<0·001). Both the long-chain inulin and an oligofructose-enriched inulin significantly lowered hepatic cholesterol concentrations compared with the control diet (P<0·05). Hepatic TAG concentrations were significantly lower in all three groups fed the fructan-supplemented diets v. the control group (P<0·0001). The results of the present study suggest that inhibition of atherosclerotic plaque formation is more potent in the presence of long-chain inulin, either alone or in combination with oligofructose (an oligofructose-enriched inulin), and that this probably is related to changes in lipid metabolism.

Butyrate is an important substrate for maintenance of colonic health and oligofructose fermentation by human faecal bacteria can increase butyrate production in vitro. However, oligofructose appears to be fermented by mainly acetate and lactate-producing bacteria rather than butyrate-producing bacteria. Isotope labelling studies using [U-13C6]glucose were used to show that 13C2 and 13C4 were the major labelled butyrate species produced from glucose fermentation, via [13C2]acetate–acetyl CoA as intermediate. Bacterial interconversion reactions were quantified and acetate conversion to butyrate and lactate conversion to acetate, propionate and butyrate were observed. Addition of oligofructose to faecal batch cultures significantly increased butyrate production. Of the newly synthesised butyrate from oligofructose fermentation, 80% was derived from interconversion of extracellular acetate and lactate, with acetate being quantitatively more significant. Carbohydrates, such as oligofructose, have prebiotic properties. In addition, oligofructose selectively stimulates the bacterial conversion of acetate and lactate to butyrate. Carbohydrates with similar properties represent a refinement of the prebiotic definition, termed butyrogenic prebiotics, because of their additional functionality.

In the present paper, we summarise the data supporting the following hypothesis: dietary inulin-type fructans extracted from chicory root may modulate the production of peptides, such as incretins, by endocrine cells present in the intestinal mucosa, this phenomenon being involved in the regulation of food intake and/or systemic effects. To test this hypothesis, male Wistar rats received for 3 weeks either a standard diet or the same diet supplemented with 10% inulin-type fructans with different degrees of polymerisation. All the effects were most pronounced with the diet containing oligofructose, and consisted of (i) a decrease in mean daily energy intake and in epididymal fat mass; (ii) a higher caecal pool of the anorexigenic glucagon-like peptide-1 (7–36) amide (GLP-1), and peptide YY (PYY), due to caecal tissue proliferation; (iii) an increase in GLP-1 and of its precursor – proglucagon mRNA – concentrations in the proximal colon; (iv) an increase in portal serum level of GLP-1 and PYY; (v) a decrease in serum orexigenic peptide ghrelin. Moreover, oligofructose supplementation improved glucose homeostasis (i.e. decreased glycaemia, increased pancreatic and serum insulin content) in diabetic rats previously treated with streptozotocin, a phenomenon that is partly linked to the reduction in food intake and that correlates with the increase in colic and portal GLP-1 content. Based on these results it appears justified to test, in human subjects, the hypothesis that dietary inulin-type fructans could play a role in the management of obesity and diabetes through their capacity to promote secretion of endogenous gastrointestinal peptides involved in appetite regulation.

Studies in rodents show that inulin and oligofructose can reduce the plasma levels of cholesterol and triacylglycerols (TG). In addition, they can oppose TG accumulation in liver and have favourable effects on hepatic steatosis. The hypotriglyceridaemic effect is due to a reduction in hepatic re-esterification of fatty acids, but mainly in the expression and activity of liver lipogenesis, resulting in lower hepatic secretion rate of TG. This repression of lipogenesis is not observed in adipose tissue. The effect on liver lipogenesis can be explained by reduced insulin/glucose levels or by a selective exposure of the liver to increased amounts of propionic acid produced in the large intestine during fermentation of non-digestible carbohydrates. The decrease in plasma cholesterol could also be due to inhibition of cholesterol synthesis by propionic acid or to modifications in the bile acid metabolism. Studies in man yield more conflicting results with a decrease or no effects on plasma lipid levels, and, when a decrease is observed, more marked effects on TG than on cholesterol and more consistent action of inulin than of oligofructose. Besides the difference in the dose of inulin or oligofructose used, differences in metabolic status could play a role in this discrepancy between man and animals since reduction in plasma TG is observed in man mainly in a situation of increased liver lipogenesis (high-carbohydrate diet, obesity, hypertriglyceridaemia). The effects on plasma cholesterol appear also more marked in hyperlipidaemic subjects than in healthy controls, suggesting that inulin and oligofructose have beneficial effects in these types of subjects.

If the primary role of diet is to provide sufficient nutrients to meet the metabolic requirements of an individual, there is an emerging rationale to support the hypothesis that, by modulating specific target functions in the body, it can help achieve optimal health. Regarding osteoporosis prevention, since Ca is most likely to be inadequate in terms of dietary intake, every strategy targeting an improvement in Ca absorption is very interesting. Actually, this process may be susceptible to manipulation by fermentable substrates. In this light, inulin-type fructans are very interesting, even if we need to gather more data targeting bone metabolism before health professionals can actively advocate their consumption to prevent senile osteoporosis. Besides targeting the prevention of postmenopausal osteoporosis, inulin-type fructans still remain a source for putative innovative dietary health intervention. Indeed, given in combination with isoflavones, they may have a potential for maintaining or improving the bone mass of human subjects, by modulating the bioavailability of phyto-oestrogens.

Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored.A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions

The rationale for supplementing an infant formula with prebiotics is to obtain a bifidogenic effect and the implied advantages of a ‘breast-fed-like’ flora. So far, the bifidogenic effect of oligofructose and inulin has been demonstrated in animals and in adults, of oligofructose in infants and toddlers and of a longchain inulin (10 %) and galactooligosaccharide (90 %) mixture in term and preterm infants. The addition of prebiotics to infant formula softens stools but other putative effects remain to be demonstrated. Studies published post marketing show that infants fed a long-chain inulin/galactooligosaccharide mixture (0·8 g/dl) in formula grow normally and have no side-effects. The addition of the same mixture at a concentration of 0·8 g/dl to infant formula was therefore recognized as safe by the European Commission in 2001 but follow-up studies were recommended. It is thought that a bifidogenic effect is beneficial for the infant host. The rising incidence in allergy during the first year of life may justify the attempts to modulate the infant's flora. Comfort issues should not be confused with morbidity and are likely to be multifactorial. The functional effects of prebiotics on infant health need further study in controlled intervention trials.

Experimental evidence on the anticancer properties of dietary prebiotics such as chicory inulin and oligofructose and dietary probiotics has accumulated in recent years. Various experimental models ranging from chemoprevention studies, tumour implantation models to genetically modified mice models, etc. have systematically shown the protective effects of these food ingredients. In some studies it appeared that synbiotics (combination of pre- and probiotics) exerted synergistic activity against processes of carcinogenesis. The logical next step in research was to find out if these observations also would be valid for human volunteers. This was the principal goal of the EU-sponsored SYNCAN project (QLK1-1999-346) which involved the integration of an in vitro study to select the most suitable synbiotic preparation, the application of this synbiotic in an in vivo rat model of chemically induced colon cancer, and, as the heart of the project, the investigation of the synbiotic effects in a human intervention study. The in vitro tests consisted of fermentation studies where the interaction of pre- and probiotics was studied. Cell-free supernatants were generated from various synbiotic combinations fermented by faecal slurry, which were then used to optimise a series of bioassays. In the rat study the anticarcinogenic effect of prebiotics and synbiotics but not of probiotics was demonstrated. Using tissue samples generated in this model, attempts were made to gain a better insight into the mechanisms underlying cancer development. The human intervention study consisted of two groups of volunteers. One group was composed of people at high risk (polypectomised subjects) for colon cancer and the other of volunteers (colon cancer subjects) who had previously undergone ‘curative resection‘ for colon cancer but were not currently receiving treatment. The present paper describes the experimental design of the SYNCAN study, and demonstrates a functional effect of the synbiotic preparation (probiotic survival during gastrointestinal transit and modification of the intestinal flora). Detailed experimental outcome of the human intervention study will be reported elsewhere.