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Gibson G.R.,University of Reading | Brummer R.J.,Orebro University | Isolauri E.,University of Turku | Lochs H.,Innsbruck Medical University | And 6 more authors.
Gut Microbes | Year: 2011

The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and metaanalyses showing evidence of beneficial effects. On the 29th and 30th of September 2010, 10 independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (1) always formulate a precise and concrete hypothesis, and appropriategoals and parameters before starting a trial; (2) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (3) ensure trials are of appropriate duration; (4) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials. © 2011 Landes Bioscience.

Zenhom M.,Max Rubner Institute | Hyder A.,Max Rubner Institute | de Vrese M.,Max Rubner Institute | Heller K.J.,Max Rubner Institute | And 3 more authors.
Journal of Nutrition | Year: 2011

Prebiotic oligosaccharides modulate the intestinal microbiota and beneficially affect the human body by reducing intestinal inflammation. This immunomodulatory effect was assumed to be bacterial in origin. However, some observations suggest that oligosaccharides may exert an antiinflammatory effect per se. We hypothesized that oligosaccharides affect the intestinal immunity via activation of peptidoglycan recognition protein 3 (PGlyRP3), which reduces the expression of proinflammatory cytokines. Caco-2 cells were treated with the oligosaccharides, α3-sialyllactose, or fructooligosaccharides (Raftilose p95), and the effects of these treatments on PGlyRP3 and PPARγ expression, the release and expression of some proinflammatory cytokines, and NF-κB translocation were tested. Both oligosaccharides had antiinflammatory activity; they significantly reduced IL-12 secretion in Caco-2 cells and gene expression of IL-12p35, IL-8, and TNFα. They also reduced the gene expression and nuclear translocation of NF-κB. Both oligosaccharides dose and time dependently induced the production of PGlyRP3, the silencing of which by transfection of Caco-2 cells with specific small interfering RNA targeting PGlyRP3 abolished the antiinflammatory role of both oligosaccharides. Incubation of Caco-2 cells with both oligosaccharides induced PPARγ. Antagonizing PPARγ by culturing the cells with GW9662 for 24 h inhibited the oligosaccharide-induced PGlyRP3 production and the antiinflammatory effect of the oligosaccharides. We conclude that oligosaccharides may exert an antiinflammatory effect by inducing the nuclear receptor PPARγ, which regulates the antiinflammatory PGlyRP3. © 2011 American Society for Nutrition.

Zenhom M.,Max Rubner Institute | Hyder A.,Max Rubner Institute | Kraus-Stojanowic I.,Max Rubner Institute | Auinger A.,Max Rubner Institute | And 3 more authors.
Immunobiology | Year: 2011

PGlyRPs recognize bacterial peptidoglycan and function in antibacterial innate immunity. Focusing on the interference between nutrition and recognition pattern proteins, free fatty acids (FFA) of dietary and bacterial sources may exert their immunological response through modulating the expression level of the PGlyRPs in enterocytes. PGlyRP3 was the only PGlyRPs member expressed in Caco2 cells. In silico analysis showed that the promoter of PGlyRP3 has some PPRE regions that, as tested by EMSA, bind physically to the PPARγ-RXRα complex. PGlyRP3 gene expression was induced by PPARγ ligands including GW1929 and some FFA. Overexpression of PGlyRP3 in Caco2 cells down regulated the expression of the inflammatory cytokines IL-8, IL-12 and TNF-α, while its silencing increased the expression of these cytokines. FFA that induced the PGlyRP3 inhibited the tested cytokines. Silencing of PGlyRP3 gene caused the same FFA to increase the cytokine gene expression. A negative regulation of NF-κB pathway, including up-regulation of Iκβ-α and down regulation of NF-κB and COX-2, is involved in the anti-inflammatory effects of PGlyRP3. In conclusion, PPARγ mediates a modulation of PGlyRP3 gene expression, which is involved in inhibiting inflammation through negative regulation of NF-κB pathway. © 2010 Elsevier GmbH.

Samuelsen A.B.C.,University of Oslo | Schrezenmeir J.,Clinical Research Center Kiel | Knutsen S.H.,Norwegian Institute of Food
Molecular Nutrition and Food Research | Year: 2014

Yeast-derived beta-glucans (Y-BG) are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. Specific preparations have received Generally Recognized as Safe status and acceptance as novel food ingredients by European Food Safety Authority. In human trials, orally administered Y-BG significantly reduced the incidence of upper respiratory tract infections in individuals susceptible to upper respiratory tract infections, whereas significant differences were not seen in healthy individuals. Increased salivary IgA in healthy individuals, increased IL-10 levels in obese subjects, beneficial changes in immunological parameters in allergic patients, and activated monocytes in cancer patients have been reported following Y-BG intake. The studies were conducted with different doses (7.5-1500 mg/day), using different preparations that vary in their primary structure, molecular weight, and solubility. In animal models, oral Y-BG have reduced the incidence of bacterial infections and levels of stress-induced cytokines and enhanced antineoplastic effects of cytotoxic agents. Protective effects toward drug intoxication and ischemia/reperfusion injury have also been reported. In conclusion, additional studies following good clinical practice principles are needed in which well-defined Y-BG preparations are used and immune markers and disease endpoints are assessed. Since optimal dosing may depend on preparation characteristics, dose-response curves might be assessed to find the optimal dose for a specific preparation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ghadimi D.,Max Rubner Institute | Hassan M.,Max Rubner Institute | Njeru P.N.,Max Rubner Institute | de Vrese M.,Max Rubner Institute | And 7 more authors.
Molecular Nutrition and Food Research | Year: 2011

Scope: Human β-defensin 2 (hBD-2) is an inducible antimicrobial peptide synthesized by the epithelium to counteract bacterial adherence and invasion. It has been suggested that probiotic bacteria sustain gut barrier function via induction of defensins. The goals of this study were (i) to evaluate the potential immunomodulatory effects of 11 different Lactobacillus fermentum strains isolated from Kimere, an African fermented pearl millet (Pennisetum glaucum) dough, on the hBD-2 secretion by human intestinal CaCo-2 cell line and (ii) to examine genetic differences between two strains of L. fermentum (K2-Lb4 and K11-Lb3) which differed in their effect on the production of hBD-2 in this study. Methods and results: Totally, 46 strains of L. fermentum from Kimere were isolated and characterized using molecular biology methods including pulsed-field gel electrophoresis patterns. After performing time- and dose-experiments, CaCo-2 cells were incubated with or without bacteria for 12h. L. fermentum PZ1162 was included as the positive control. Cell-free supernatants were analyzed for hBD-2 protein by enzyme-linked immunosorbent assay (ELISA). To identify potential bacterial genes associated with hBD-2 regulation, suppression subtractive hybridization (SSH) was used. Among the 11 strains tested, only two strains of bacteria, K11-Lb3 and K2-Lb6, significantly induced the production of hBD-2 by CaCo-2 cells. This effect was strain-specific, dose-dependent and particularly seems to be bacterial genomic-dependent as manifested by SSH. L. fermentum strains with and without hBD-2 inducing effect differed in genes encoding proteins involved in glycosylation of cell-wall proteins e.g. glycosyltransferase, UDP-N-acetylglucosamine 2-epimerase, rod shape-determining protein MreC, lipoprotein precursors, sugar ABC transporters, and glutamine ABC transporter ATP-binding protein. Conclusion: This study implies that certain strains of L. fermentum isolated from Kimere may stimulate the intestinal innate defense through the induction of hBD-2. The molecular basis of hBD-2 induction by L. fermentum strain K11-Lb3 may be based on glycosylated cell-surface structures synthesized with the aid of glycosyltransferase, UDP-N-acetylglucosamine 2-epimerase, and rod shape-determining protein MreC. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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