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The International Scientific Conference on Probiotics and Prebiotics Expert Rev. Gastroenterol. Hepatol. 5(5), 571–573 (2011)
Karen Madsen Division of Gastroenterology, Department of Medicine, University of Alberta, 7–142 Katz Group Center, Edmonton, AB T6G 2N1, Canada Tel.: +1 780 492 5257 Fax: +1 780 492 7593
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The International Scientific Conference on Probiotics and Prebiotics Kosice, Slovakia, 14–16 June 2011 The 5th International Scientific Conference on Probiotics and Prebiotics was held in the Doubletree Hotel in Kosice, Slovakia, and highlighted current advances in the research and use of probiotics and prebiotics in both animal and human health. The conference attracted academic and industry representatives from over 35 countries and facilitated networking between research scientists and industry. A poster session was on display throughout the entire meeting. Over the course of the 3-day symposium, 12 sessions addressed issues related to the use of probiotics and prebiotics in the prevention and treatment of chronic and infectious diseases, their effects on host immune function and how they may modulate existing gut microbes. Keywords : Bifidobacteria • immunity • inflammation • Lactobacillus • prebiotics • probiotics
Metabolic syndrome, cancer & cardiovascular health
In the first session, the keynote lecture was delivered by Alojz Bomba (Institute of Experimental Medicine, Pavol Jozek Safarik University, Kosice, Slovakia), who discussed the similarities in atherosclerosis and cancer pathogenesis and progression, and how probiotics, prebiotics and natural bioactive substances could be used as preventative measures to modulate common pathways in these conditions. Min-Tze Liong (Universiti Sains Malaysia, Penang, Malaysia) expanded upon these concepts and reviewed existing evidence for the use of probiotics in the prevention of cancer and possible mechanisms related to a probiotic-induced reduction in risk. Overall, it was concluded that while there is strong experimental evidence to support a role for probiotics and prebiotics in the reduction of colon carcinogenesis, more clinical trials are required to positively show a benefit [1] . Wilhelm Holzapfel (Handong Global University, Pohang, South Korea) discussed the relationship between serum cholesterol and cardiovascular disease and examined the current experimental data showing some strains of Lactobacilli to reduce serum low-density lipoprotein and cholesterol. It was shown that www.expert-reviews.com
10.1586/EGH.11.61
some Lactobacillus strains may reduce cholesterol absorption through the downregulation of Niemann–Pick C1-like protein (NPC1L1) [2] . Work presented by Yasuhiro Nakano (Tokai University School of Medicine, Isehara, Japan) provided evidence that gut microflora could be involved in modulating or initiating the metabolic syndrome through the induction of hypercholesterolemia. Using human flora-associated and a high cholesterol-fed mouse models, Nakano showed that hypercholesterolemia was associated with an increase in Clostridium innocuum, and further, that Lactobacillus johnsonii could significantly attenuate serum cholesterol and liver steatosis in the high cholesterol-fed mice. Gut–brain axis & behavior
Peter McLean (Nestle Research Center, Switzerland) discussed the evidence related to the ability of the gut microflora to modulate digestive comfort and behavior. Clinical data have shown that selected probiotic strains can alter mood (Lactobacillus helveticus and Bifidobacterium longum) and further, other strains have demonstrated benefit in the treatment of irritable bowel disease (Bifidobacterium infantis) [3] . Data were presented showing that
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treatment of Trichur muris-infected mice with B. longum was effective in normalizing anxiety-like behavior exhibited by the infected mice and also in increasing brain-derived neurotrophic factor [4] . This effect of B. longum required an intact vagus nerve and did not involve modulation of gut immune function [4] . Another series of experiments examining the effects of gut microflora on animal behavior was presented by Ryo Nishino (Tokai University School of Medicine, Kanagawa, Japan). In these studies, germ-free mice were colonized by microflora from specific pathogen-free mice or B. infantis and male offspring were examined from 7 to 16 weeks of age. It was found that the type of colonization significantly affected both the activity and anxiety of the mice. Immunity
Several sessions were devoted to the effects of probiotics and prebiotics on host immune parameters in both animal models and human clinical studies. Yoshikatsu Murooka (Hiroshima Institute of Technology, Hiroshima, Japan) described the effects of Lactobacillus plantarum L-137 on spleen cells and peritoneal macrophages and showed that a specific structure of lipoteichoic acid was an important factor in inducing cytokine secretion. Further, expression vectors for cholesterol-degrading enzymes, dust mite allergens and cedar pollen allergen were expressed in cells of L. plantarum NCL21, a derivative of L-137. Oral vaccination in a mouse model of pollinosis prevented pollinosis-like nasal symptoms and suppressed allergen-specific IgE responses and IL-4 production, suggesting that this may be a feasible method for desensitization to specific types of allergens. Data using a mixture of probiotics to generate regulatory dendritic cells were presented by Sin-Hyeog Im (Gwangju Institute of Science and Technology, Gwangju, South Korea) [5] . It was shown that this mixture of probiotic strains could generate regulatory dendritic cells, which, in turn, were able to convert effector CD4 T cells into Foxp3 + Treg cells, providing a mechanism for the ability of certain probiotic strains to modulate host immunity. Ryo Aoki (Glico Dairy Products, Japan) presented data from a randomized double-blind placebo-controlled trial looking at the effects of kestose, a fructo-oligosaccharide, in infants with atopic dermatitis. After 12 weeks of treatment, there was a reduction in clinical manifestations in the prebiotic-treated group; however, this improvement did not correlate with increases in bifidob acteria, suggesting another possible mechanism. In vitro studies in Caco-2 cells showed that addition of kestose to cells resulted in an increase of monolayer resistance, suggesting a possible direct effect of kestose on gut barrier function. Another study presented by Pavel Chernyshov (National Medical University, Kharkiv, Ukraine) examined the effects of a 30 day administration of Lactobacillus rhamnosus (Lacidofil®) in children with atopic dermatitis. A reduction in clinical severity of symptoms occurred in 63% of the children receiving the probiotic compared with 32% in the placebo group. Clinical and immunological effects of Bifidobacterium lactis supplementation were studied in a double-blind placebo-controlled trial over a period of 150 days in a population of healthy active 572
adults. As presented by Nicholas West (Griffith University, QLD, Australia), upper respiratory tract illness was 27% less in subjects consuming B. lactis, and subjects had fewer total days of cold and flu medication usage compared with those on placebo, suggesting clinically beneficial effects. Data presented by Eric Guillemard (Danone Research, France) examining the effects of a fermented milk product containing Lactobacillus casei on various target populations (children, students under stress, soldiers, aging populations and postpartum women) demonstrated clear effects of this strain on numerous host immune functions, and it was suggested that dietary intervention using this particular strain may be efficacious in reducing infections [6,7] . Karen Madsen (University of Alberta, AB, Canada) discussed the current evidence for the use of probiotics in the treatment of inflammatory bowel disease, and concluded that, at this time, there is evidence for the use of selected strains in the maintenance of remission in patients with ulcerative colitis, but no evidence to support their use in patients with Crohn’s disease. Immunity & infection
A keynote lecture presented by Arthur Ouwehand (Danisco Sweeteners, Finland) examined the efficacy of probiotics in preventing antibiotic-associated diarrhea. Clinical data were presented from a triple-blinded randomized placebo-controlled trial using both a low dose (2.5 × 109 colony forming units [cfu]/day) and a high dose (1010 cfu/day) of a probiotic preparation containing Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, B. lactis BL-04 and B. lactis Bi-07 in patients consuming antibiotics. A clear dose response was observed, with the high dose significantly reducing the incidence of both antibiotic associated diarrhea and clostridum-induced diarrhea. A reduction in abdominal pain, number of liquid stools and duration of diarrhea was also observed. Clinical data presented by Flore Depeint (Institute Polytechnique LaSalle Beauvais, Beauvais, France) showed that in a parallel double-blind clinical trial, healthy subjects consuming maltodextrin (placebo) or a mixture of inulin (Fibruline®) combined with arabinoxylane (Opti’Flor®) for 4 weeks resulted in an increase in levels of fecal secretory IgA and a reduction in serum lipopolysaccharide in the subjects consuming the prebiotic. This was associated with altered gut microflora and an enhanced responsiveness in lipopolysaccharide-stimulated whole blood. Another study presented by Depeint demonstrated further evidence for a prebiotic-induced modulation of intestinal immune function. Male piglets fed low-digestive carbohydrate (4% wheat dextrin) or placebo were challenged with trinitobenzene sulfonic acid. The piglets receiving the prebiotic had increased stool secretory IgA, increased levels of Bifidobacterium and Fusobacterium, and reduced intestinal injury. Interesting work presented by Shinji Fukuda (Riken RCAI, Japan) utilized an integrated ‘omics’ approach in a mouse model of enterohemorrhagic Escherichia coli 0157:H7 infection to demonstrate that specific strains of bifidobacteria were effective in preventing the lethal effects of enterohemorrhagic E. coli infection Expert Rev. Gastroenterol. Hepatol. 5(5), (2011)
The International Scientific Conference on Probiotics & Prebiotics
through an enhanced production of acetate [8] . This production of acetate was related to the presence of genes encoding ATPbinding cassette-type transporters for carbohydrate transport in the effective bifidobacteria strains and involved an acetateinduced enhancement of intestinal epithelial barrier function and reduction of Shiga toxin translocation [8] . Carlos Lifschitz (Hospital Italiano, Buenos Aires, Argentina) discussed the current evidence for a therapeutic efficacy for Saccharomyces boulardii. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of anti biotic-associated diarrhea and traveler’s diarrhea. Randomized trials also support the use of this probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms [9] . Gastric health
Clinical data were presented by Natalia Baryshnikova (St Petersburg State Medical Academy, Russian Federation, Russia) showing that, in patients with chronic gastritis associated with H. pylori, monotherapy with Bacillus subtilis and Enterococcus faecium was effective in reducing gastritis. Although the rate of eradication was lower in the probiotic-treated group compared with the group receiving standard eradication therapy (~40% compared with ~60%), the probiotic treated group had less changes in colonic microflora. Other information presented in this session by Yasuhiro Koga (Tokai University School of Medicine, Tokyo, Japan) included the findings that both lactobacilli and H. pylori affect the development of gastric muscle and regulated gastrin-mediated gastric acid secretion. Vaginal health
Gregor Reid (Lawson Health Research Institute, ON, Canada) analysed the vaginal microbiome of pre- and post-menopausal women using Illumina sequencing of the 16S rRNA gene and
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Ooi LG, Liong MT. Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. Int. J. Mol. Sci. 11(6), 2499–2522 (2010). Huang Y, Wang J, Cheng Y, Zheng Y. The hypocholesterolaemic effects of Lactobacillus acidophilus American type culture collection 4356 in rats are mediated by the downregulation of Niemann–Pick C1-like 1. Br. J. Nutr. 104(6), 807–812 (2010). Moayyedi P, Ford AC, Talley NJ et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59(3), 325–332 (2010). Bercik P, Verdu EF, Foster JA et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters
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correlated the results with a full transcriptome analysis using Affymetrix GeneChip™ Human microarrays in a subset of women. Overall, it was found that in healthy subjects, Lactobacillus iners and Lactobacillus crispatus were the most abundant and that postmenopausal women had stability in their microbiotia abundance profiles over time. Conclusion
The goal of this conference was to provide a scientific forum for both academic and industry interests and to facilitate networking for the participants. On these fronts, the symposium could be considered a great success. The conference attracted registrants from over 35 countries and leading scientists presented current advances in both clinical effectiveness and basic science related to mechanisms of action of probiotics and prebiotics in both in vitro and in vivo experimental models. The overall program focused on advances in the use of probiotics and prebiotics to maintain health and prevent disease and provided ample opportunities for discussion. The symposium dinner held in Dolna Brana (Lower Gate; Kosice, Slovakia) was truly a unique experience and allowed not only for networking, but also the exploration of the original gateway to the city, which included an intricate system of medieval fortifications and town walls dating back to the 13th Century. The next conference will be held in 2012 in the same venue and promises to be an even greater success. Financial & competing interests disclosure
Karen Madsen has received grants from: Alberta Innovates, Crohn’s and Colitis Foundation of Canada and Canadian Institutes for Health Research. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
central nervous system biochemistry in mice. Gastroenterology 139(6), 2102–2112.e1 (2010).
References 5
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Kwon HK, Lee CG, So JS et al. Generation of regulatory dendritic cells and CD4 +Foxp3 + T cells by probiotics administration suppresses immune disorders. Proc. Natl Acad. Sci. USA 107(5), 2159–2164 (2010). Guillemard E, Tanguy J, Flavigny A, De La Motte S, Schrezenmeir J. Effects of consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 on common respiratory and gastrointestinal infections in shift workers in a randomized controlled trial. J. Am. Coll. Nutr. 29(5), 455–468 (2010).
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Guillemard E, Tondu F, Lacoin F, Schrezenmeir J. Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial. Br. J. Nutr. 103(1), 58–68 (2010).
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Fukuda S, Toh H, Hase K et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469(7331), 543–547 (2011).
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Mcfarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J. Gastroenterol. 16(18), 2202–2222 (2010).
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