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Commensal gut microbiota and probiotics have numerous effects on the host's metabolic and protective systems, which occur primarily through the intestinal epithelial cell interface. Prebiotics, like galacto-oligosaccharides (GOS) are widely used to modulate their function and abundance. However, important structure-function relations may exist, requiring a detailed structural characterization. Here, we detailed the structural characterization of bovine whey derived oligosaccharide preparations enriched with GOS or not, dubbed GOS-enriched milk oligosaccharides (GMOS) or MOS, respectively. We explore GMOS's and MOS's potential to improve intestinal epithelial barrier function, assessed in a model based on barrier disruptive effects of the Clostridioides difficile toxin A. GMOS and MOS contain mainly GOS species composed of β1-6- and β1-3-linked galactoses, and 3'- and 6'-sialyllactose. Both GMOS and MOS, combined with lactobacilli, like Lactobacillus rhamnosus (LPR, NCC4007), gave synergistic epithelial barrier protection, while no such effect was observed with Bifidobacterium longum (BL NCC3001), Escherichia coli (Nissle) or fructo-oligosaccharides. Mechanistically, for barrier protection with MOS, (i) viable LPR was required, (ii) acidification of growth medium was not enough, (iii) LPR did not directly neutralize toxin A, and (iv) physical proximity of LPR with the intestinal epithelial cells was necessary. This is the first study, highlighting the importance of structure-function specificity and the necessity of the simultaneous presence of prebiotic, probiotic and host cell interactions required for a biological effect.

Fructooligosaccharides (FOS) are considered prebiotics because of their ability to promote growth of specific beneficial gut bacteria, such as bifidobacteria. Some studies reported potential immune-modulating properties. The aim of this study was to investigate the effect of FOS:inulin mix on murine response to Salmonella vaccine and evaluate the relevance toward protection against Salmonella infection. Balb/c mice were fed a diet containing 5% FOS:inulin mix or a control diet 1 wk before oral immunization with a suboptimal dose of live attenuated Salmonella typhimurium vaccine. Four weeks after vaccination, mice were infected with LD100 of virulent S. typhimurium. Specific blood Salmonella immunoglobulin G and fecal immunoglobulin A significantly increased in mice fed the diet containing prebiotics compared with control mice 4 wk postimmunization. Peritoneal macrophage phagocytic activity also significantly increased in FOS:inulin-fed mice at 1 wk postimmunization compared with control mice. No detectable effects were observed on the percentage of lymphoid cell subsets in the spleen. However, production of cytokines, interferon-gamma, interleukin-12, and tumor necrosis factor alpha, was numerically increased in spleen cell cultures stimulated with mitogens from FOS:inulin-fed mice 1 and 4 wk postimmunization. Salmonella translocation to lymphoid organs was not affected by feeding FOS:inulin. However, the improved response to Salmonella vaccine was concomitant with an increase in the survival rate of FOS:inulin-fed mice upon challenge with virulent Salmonella. No detectable effects were observed on the composition or the metabolic activity of the microbiota. Overall, the data suggest that a diet supplemented with FOS:inulin mix stimulates mucosal immunity and seems to improve efficacy of an oral vaccine.

According to Burkitt's hypothesis, dietary fibres may protect against the development of colorectal cancer. In rats, studies have shown that only butyrate-producing fibres are protective. In parallel, in humans, non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to display a protective effect against colorectal cancer. Among them, COX-2-selective inhibitors which present less side effects than non-selective agents, are promising as chemopreventive agents. Our aim was to analyse the effect of an association between butyrate-producing fibres and the COX-2 inhibitor on the development of aberrant crypt foci (ACF) in rats. Fisher F344 rats were fed with (1) a standard low fibre control diet; (2) the standard diet supplemented with 1500 ppm celecoxib; (3) a diet supplemented with 6% fructo-oligosaccharide (FOS); and (4) a diet with both celecoxib and FOS. Three weeks later, the rats were injected twice with azoxymethane and the number of ACF was determined 15 weeks later. In the control group, 43.8 +/- 6.4 ACF were found. This number was not significantly modified by the addition of FOS or celecoxib alone to the diet. However, the association of FOS and celecoxib resulted in a 61% reduction in the number of ACF (P < 0.01). The number of aberrant crypt per foci was also reduced. Thus, although no significant effect of celecoxib or FOS alone was identified, the association of butyrate-producing fibre and celecoxib was effective in preventing the development of ACF. This preliminary study argues for a strong protective effect of such an association which deserves further studies.

Fructooligosaccharides (FOS) increase the growth of lactic acid bacteria (LAB) and promote butyrate and lactate production. Because of these properties, FOS may benefit intestinal inflammation. The purpose of this study was to investigate the effect of FOS on colitis in rats and determine which factors are involved. Groups of rats with intracolonic trinitrobenzene sulfonic acid (TNBS)-induced colitis received intragastric infusions of 9 g/L NaCl, 1 g/d FOS or 10(11) colony-forming units (cfu)/d LAB (Experiment 1), or intracolonic infusions of 9 g/L NaCl, butyrate, lactate or butyrate + lactate with or without 10(9.5) cfu/d LAB (Experiment 2). Each infusion was administered twice daily for 14 d. Intragastric FOS reduced the gross score for inflammation (P < 0.001), myeloperoxidase (MPO) activity (P < 0.001) and pH (P < 0.001), and increased lactate (P = 0.02) and butyrate concentrations (P < 0.001) as well as LAB counts in the cecum (P < 0.01). Intragastric LAB (10(11) cfu/d) had the same beneficial effects as FOS and modified the cecal composition similarly. High doses of intracolonic butyrate and lactate reduced the indices of inflammation (P < 0.001), whereas administration of the lower concentrations found in the colon tended to decrease (P < 0.1) the gross score for inflammation and MPO activity. Addition of LAB (10(9.5) cfu/d) to the organic acids was necessary to reproduce the significant FOS-induced effects on these variables. Thus, under the experimental conditions used, FOS reduced intestinal inflammatory activity mainly by increasing LAB counts in the intestine.

Aims: In vitro studies have suggested that fructo-oligosaccharides (FOS) and resistant starch (two fermentable non-digestible carbohydrates) display different fermentation kinetics. This study investigated whether these substrates affect the metabolic activity and bacterial composition of the intestinal microflora differently depending on the caecocolonic segment involved., Methods and Results: Eighteen rats were fed a low-fibre diet (Basal) or the same diet containing raw potato starch (RPS) (9%) or short-chain FOS (9%) for 14 days. Changes in wet-content weights, bacterial populations and metabolites were investigated in the caecum, proximal and distal colon and faeces. Both substrates exerted a prebiotic effect compared with the Basal diet. However, FOS increased lactic acid-producing bacteria (LAPB) throughout the caecocolon and in faeces, whereas the effect of RPS was limited to the caecum and proximal colon. As compared with RPS, FOS doubled the pool of caecal fermentation products, while the situation was just the opposite distally. This difference was mainly because of the anatomical distribution of lactate, which accumulated in the caecum with FOS and in the distal colon with RPS. Faeces reflected these impacts only partly, showing the prebiotic effect of FOS and the metabolite increase induced by RPS., Conclusions: This study demonstrates that FOS and RPS exert complementary caecocolonic effects., Significance and Impact of the Study: The RPS and FOS combined ingestion could be beneficial by providing health-promoting effects throughout the caecocolon.

Dietary fibre consists of remnants of edible plant cell polysaccharides and associated substances resistant to hydrolysis by human alimentary enzymes, which may benefit health through a wide range of physiological effects. Inulin and oligofructose are storage carbohydrates found in a number of vegetables, fruits and whole grains. They resist digestion and absorption in the stomach and small intestine of humans, as shown by their almost full recovery at the end of the ileum of healthy or ileostomised volunteers. Inulin and oligofructose thus enter into the large intestine where they are available to fermentation, as demonstrated by increased breath hydrogen. Fermentation of both substrates is complete and no residue is found in human stools. Inulin and oligofructose improve laxation. Their bulking capacity comprised between 1.2 and 2.1 g of stool per g of ingested substrate, results mainly from increases in microbial biomass in the colon. As water content of bacterial cells is high, stools are softer and easier to expulse. Stool frequency is thus increased, particularly in slightly constipated individuals. In addition, likely due to their fermentation properties, inulin and oligofructose also affect the intestinal epithelium (trophicity, mucin expression, etc.), that may strengthen mucosal protection and reduce the risk of gastrointestinal diseases. In summary, inulin and oligofructose are plant carbohydrates, resistant to digestion in the human small intestine and fermented by colonic bacteria. They exert several intestinal physiological effects contributing to maintenance of health. Therefore, inulin and oligofructose fit well within the current concept of dietary fibre.

While the prebiotic effects of fructo-oligosaccharides (FOS), short-chain polymers of fructose, have been thoroughly described after 2-3 wk of ingestion, effects after intake for several months are unknown. We tested the hypothesis that these effects would differ after ingestion for short and long periods in rats. Rats were fed a basal low-fiber diet (Basal) or the same diet containing 9 g/100 g of FOS for 2, 8 or 27 wk, and cecal contents were collected at the end of each time period. Cecal short-chain fatty acid concentration was higher in rats fed FOS than in those fed Basal, and this effect persisted over time: 83.8 +/- 4.1 vs. 62.4 +/- 6.5 micromol/g at 2 wk and 103.5 +/- 5.8 vs. 73.2 +/- 7.4 micromol/g at 27 wk (P < 0.05). The molar butyrate ratio was higher in rats fed FOS regardless of the time period (14.8 +/- 0.6% vs. 6.7 +/- 1.1% at 27 wk, P < 0.05). Lactate concentration in rats fed FOS was elevated after 2 wk and then decreased: 63.5 +/- 21.6 micromol/g at 2 wk vs. 8.8 +/- 3.3 micromol/g at 8 wk (P < 0.05). After 2 wk, FOS increased the concentrations of total lactic acid-producing bacteria, and Lactobacillus sp. (P < 0.05), without modifying total anaerobes. However, most of these effects were abolished after 8 and 27 wk of FOS consumption. In the long term, the FOS-induced increase in intestinal lactic acid-producing bacteria was lost, but the butyrogenic properties of FOS were maintained.