Structure and Function of Bovine Whey Derived Oligosaccharides Showing Synbiotic Epithelial Barrier Protective Properties.

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.

Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

Background & Aims: Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms.

Methods: AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics.

Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation.

Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule.

Biomarkers of human gastrointestinal tract regions.

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations.

Panorganismal gut microbiome-host metabolic crosstalk.

Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale.

Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model.

Gut microbiome-host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic microbiome-mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ-free mice inoculated with a model of human baby microbiota.

Feeding a diet containing a fructooligosaccharide mix can enhance Salmonella vaccine efficacy in mice.

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.

Multifaceted transcriptional regulation of the murine intestinal mucus layer by endogenous microbiota.

The intestinal mucus layer and endogenous microbiota are strongly intertwined and this contributes to the maintenance of the epithelial barrier and ultimately of gut homeostasis. To understand the molecular foundations of such relationship, we investigated if the nature of the microbiota transcriptionally regulates mucus layer composition in vivo. We found that the expression of mucins 1 to 4 and trefoil factor 3 was down-regulated in the ileum and colon of conventional and reconventionalized mice compared with germ-free animals.

In vitro prebiotic effects of Acacia gums onto the human intestinal microbiota depends on both botanical origin and environmental pH.

Acacia gums are commonly used food additives. It is currently unclear how extensively these non-digestible polysaccharides are fermented in the human large intestine. However, they have been shown to support bifidobacterial growth in vitro and may represent useful candidate prebiotics.

Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats.

Objectives: Psychological stress during the neonatal period results in intestinal barrier dysfunction and growth alterations later in life. We aimed to restore impaired barrier function and growth rate by a nutritional intervention.

Methods: Male rat pups (n = 84) were assigned to 1 of 2 rearing conditions from postnatal day (PND) 2 to PND14: S, separated 3 h/d from their mothers, or H, 15 min/d handled controls.

MUC genes are differently expressed during onset and maintenance of inflammation in dextran sodium sulfate-treated mice.

Colonic mucosal protection is provided by mucous gel, mainly composed of secreted (Muc2) and membrane-bound (Muc1, Muc3, Muc4) mucins. Our aim was to determine the expression profile of secreted and membrane-bound mucins in experimental dextran sulfate sodium (DSS)-induced colitis. Acute colitis was induced in Balb/C mice by oral administration of 1.

The VSL# 3 probiotic mixture modifies microflora but does not heal chronic dextran-sodium sulfate-induced colitis or reinforce the mucus barrier in mice.

The mucus layer covering the epithelium is one of the main lines of defense of the colonic barrier. Both mucus gel and mucin expressions are altered during colonic inflammation and could be involved in epithelial repair. We postulated that modulating colonic mucus and mucins by probiotic supplementation could contribute to healing inflammatory mucosa.

Neonatal antibiotic treatment alters gastrointestinal tract developmental gene expression and intestinal barrier transcriptome.

The postnatal maturation of the gut, partially modulated by bacterial colonization, ends up in the establishment of an efficient barrier to luminal antigens and bacteria. The use of broad-spectrum antibiotics in pediatric practices alters the gut bacterial colonization and, consequently, may impair the maturation of the gut barrier function. To test this hypothesis, suckling Sprague-Dawley rats received a daily intragastric gavage of antibiotic (Clamoxyl; an amoxicillin-based commercial preparation) or saline solution from postnatal day 7 (d7) until d17 or d21.

Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident.

Aim: To assess the role of lactate as a precursor for butyrate biosynthesis in human colonic microflora.

Methods And Results: Three human faecal microfloras were incubated in vitro with media supplemented with 30 mmol l(-1) unenriched or 13C-enriched lactate. Lactate metabolism and short-chain fatty acid (SCFA) production were quantified.

Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose.

The mucus layer covering the gastrointestinal mucosa is considered the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a short-chain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion.

Adaptation to low-protein diet increases inhibition of gastric emptying by CCK.

Chronic nutritional disorders such as protein malnutrition are associated with delayed gastric emptying and increased postprandial cholecystokinin (CCK) levels. This study investigated the mechanisms involved in gastric emptying adaptation to low-protein diet. Two groups of 12 rats were adapted to a low-protein (LPD) or standard diet (SD) for 3 weeks.

Fructooligosaccharide associated with celecoxib reduces the number of aberrant crypt foci in the colon of rats.

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.

Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases.

Background: Leptin, a protein with a cytokine-like structure, is produced predominantly by adipocytes. It appears to play a key role in immune responses by increasing the secretion of Th1 and pro-inflammatory cytokines. As fat-wrapping is a characteristic feature of Crohn's disease (CD), and as increased leptin levels have been reported in animal models of intestinal inflammation, this study investigated whether mesenteric adipose tissue could be a source of leptin in human inflammatory bowel disease (IBD).

Prebiotics: actual and potential effects in inflammatory and malignant colonic diseases.

Purpose Of Review: This paper will summarize the most recent clinical and experimental data on the effects of prebiotics in inflammatory and cancerous diseases of the large intestine.

Recent Findings: Animal studies, as well as data obtained in in-vitro cell culture systems, have underlined the potential of certain prebiotics to protect against inflammatory and cancerous processes in the large intestine. Clinical trials are now in progress to assess the relevance of these promising results.

New scientific paradigms for probiotics and prebiotics.

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics.

Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation.

Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferation in vitro and in vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect.

Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract.

Short-chain fatty acids (SCFA) affect local and remote motility of the gastrointestinal tract by mechanisms that are not completely understood. In the large intestine where they are produced, they inhibit peristaltic activity and may stimulate tonic activity. When present in the terminal ileum as a result of reflux of colon contents, they elicit propulsive contractions.

Three-dimensional binding of epidermal growth factor peptides in colonic tissues produced from rotating bioreactor.

Epidermal growth factor peptide binding was analyzed on primary cultures of colonic cells and along crypts by fluorescent laser-scanning confocal microscopy, using a three-dimensional image analysis software (Quant3D, Linux/Unix). Structural, proliferative units from primary cultures grown in rotating bioreactor for 41 d were arranged according to a tubular symmetry or on a parallelepiped sheet. Mean width, height, and depth of 23 tissue-like masses (+/- standard error) were 125 microm (+/-16), 152 microm (+/-23), and 29 microm (+/-3), respectively.

Raw potato starch and short-chain fructo-oligosaccharides affect the composition and metabolic activity of rat intestinal microbiota differently depending on the caecocolonic segment involved.

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.