æConference summary Probiotics in gastric and intestinal disorders as functional food and medicine Nils-Georg Asp, Roland Mo¨llby, Lisa Norin and Torkel Wadstro¨m The chairman of the first session, Tore Midtvedt, scribed as the dominant indigenous lactobacilli of opened the conference by reminding the audience the human intestine. From 130 intestinal biopsies that since ancient time, food, bowel and health have the following lactobacilli were cultured: 38% L been interrelated medical topics. Microorganisms, gasseri, 20%, L fermentum, 8% L crispatus, 7% L especially lactobacilli and some yeasts, have been rhamnosus, 4.4% L salivarius and 4.4% L mucosae- used as health-promoting agents since ancient time. like probiotic strains (unpublished data). Versalovic Metchnikoff suggested that the long healthy life of stressed that there is a demand for a more detailed Bulgarian peasants resulted from consumption of understanding of the composition of the commensal fermented milk products. The term ‘‘probiotic’’ is intestinal microbiota and their interactions with the still under debate. In all definitions there are two intestinal immune system, which would create prerequisites: 1) the microbes have to be alive, and breakthroughs in probiotic research. Gene and 2) the microbes are given for other than nutritional protein discovery efforts with defined clones of reasons, i.e., it is not the caloric or nutrient content specific intestinal lactobacilli and other lactic acid of the probiotics that counts. ME Sanders’ defini- bacteria would lead to the unravelling of mechan- tion from 1996 says that probiotics, simply defined, isms of probiosis and development of new thera- are microbes consumed for health effects. The term peutic strategies with such probiotic bacteria. These probiotics is used in food applications, and biother- could be achieved by apeutics is often used in clinical applications. In selecting probiotic/biotherapeutic strains, Midtvedt . A detailed mapping of lactic acid bacteria in the emphasised the importance of thinking function mammalian intestine rather than disease, and of investigating functions in . Clone-based investigations of commensal mi- specified compartments of the body. For instance, b crobes and of the functions of different probio- glucuronidase activity of the colonic microflora may tics modify conjugation of endo- and exogenous sub- stances, and the presence of cytochrome P 450 in The question is raised whether one can alter or human intestinal flora may influence the expression restore the microbial balance in human individuals. of hepatic cytochrome P 450. And does restoration of a microbial balance lead to restoration of an immunologic balance? The gastrointestinal microflora Go¨ ran Molin reviewed recent work on the intest- James Versalovic presented an overview of the inal microflora, in collaboration with B. Jeppsson, intestinal microflora. A number of Lactobacillus S. Ahrne´ and M. Wang. By the use of phenotypical species colonise the stomach and intestine immedi- identification methods and anaerobic culture tech- ately after birth, adhere to epithelial cells and niques, the GI-flora has been reported to be become a part of the stable intestinal flora during dominated by genera such as Bacteroides, Eubac- development and adulthood. The genus Lactoba- terium, Clostridium, Ruminococcus, Peptococcus, cillus includes more than 60 different species, and Peptostreptococcus, Bifidobacterium and Fusobac- has received attention as a source for probiotic terium. However, culture-based methods provide an agents and protein delivery systems for the mam- incomplete assessment of the bacterial GI-flora and malian intestine. Only few species have been de- phenotypic features are not always reliable or Scandinavian Journal of Nutrition 2004; 48 (1): 15Á25 # 2004 Taylor & Francis ISSN 1102-6480 15 DOI: 10.1080/11026480410028968 Asp N-G et al. sufficiently descriptive in bacterial systematics. Sixty ing oesophageal adenocarcinoma. How to reduce to eighty percent of the GI-bacteria have been the discomfort/problems in dyspepsia subjects? The claimed to be unculturable. One way to circumvent most important way to achieve improvement is by a the need for cultivation is the use of DNA lifestyle modification, e.g. by reducing use of amplification by PCR and subsequent cloning of tobacco, alcohol and coffee, and weight reduction 16S rRNA genes, followed by comparisons with by an overall dietary alteration. Patients with a available databases. Microbes that are in close Helicobacter pylori (H.p) infection were formerly contact with the body are more likely to interact also included in this group. Thus 25Á30% of middle- with human physiology, and this part of the flora of aged patients with earlier diagnosed reflux problems the GI tract may be involved in developing chronic have been identified as H.p patients. After eradica- inflammation and colon cancer. It can also be tion of the infection, there was surprisingly a affected by antibiotics, cytotoxic drugs and radio- significantly higher risk of GORD symptoms in therapy, trauma, and intensive care therapy. It is one study, but the disease signs had almost totally thus important to map the mucosa-associated flora disappeared two years after the H.p eradication in a in healthy individuals in order to clarify the group of almost 1700 subjects, and the risk of pathogenic risk under stressed and other disturbed relapse was also strongly reduced. Lundell’s overall conditions in man, before one tries to perform conclusion was that the benefit of eradicating H.p in similar studies in diseased subjects. non-ulcer dyspepsia and GORD is greater than the possible risks. Dyspepsia, gastric reflux disease and gastric cancer The state of the art regarding probiotics and F. Bazzoli introduced this subject by stating that Helicobacter pylori gastritis was reviewed by A. epidemiological investigations in the US show that Gasbarrini, whose full paper is published in this 25% of the population suffer from recurrent dys- issue of the Scandinavian Journal of Nutrition (pp. pepsia, but less than 50% seek medical treatment for 26Á31). Proposed mechanisms of action of oral their symptoms. These symptoms have, however, a bacteriotherapy include synthesis of antimicrobial significant impact on the quality of life. Dyspepsia substances such as organic fatty acids, ammonia, is defined as pain or discomfort from the upper hydrogen peroxide and bacteriocines, a competitive abdomen. In practice, there is considerable overlap interaction with pathogens for ‘‘space and food’’, of dyspepsia and gastro-oesophageal reflux disease through the use of available nutrients and occupa- (GORD/GERD). A key element to effectively tion of microbial adhesion sites, modification of managing patients with dyspeptic symptoms is the toxins or toxin receptors, and immuno-modulation. identification and exclusion of GORD through H. pylori is one of the most prevalent infectious proton pump inhibitor (PPI) therapy to dyspeptic agents worldwide and has been indicated as one persons. These are individuals who are exposed to pathogenic factor in the development of chronic the risk of physical complications or who experience gastritis, peptic ulcer disease and gastric malignan- clinically significant impairment of health-related cies. One suggested mechanism related to probiotic well-being due to episodes of GORD (after reassur- therapy is that Lactobacilli spp. are supposed to ance). A probiotic treatment approach in relation to adhere and even transiently reside in the stomach, GI disorders, aiming to restore or alter/balance the enhance the immune response and reduce the H. intestinal microflora, might have an anti-inflamma- pylori inflammation effect on the host gastric tory effect, could reduce gas production, could mucosa. Furthermore, probiotics have been shown promote intestinal motility and could have a visceral to improve patients’ compliance with antibiotic analgesic effect. Moreover, by including prebiotics, treatment by reducing side effects. a proximal colon dysfunction might be corrected via Y. Koga, together with A. Tamura, K. Kobayashi carbohydrate fermentation. The proximal gastric and A. Takagi, presented studies on H. pylori tone could also be inhibited with a role in the inhibition in experimental animals and man. Lac- regulation of gastric motility. tobacilli are the dominant bacteria found in the Lars Lundell described GORD as ‘‘a burning fasting stomach although their number is small. feeling rising from your stomach or lower chest up However, it increases by a factor of thousands in towards the neck’’. There is one major concern with individuals with low gastric acidity, suggesting that dyspepsia Á an increased risk with time of develop- the stomach is potentially an organ which lactoba- 16 Conference summary cilli may colonise in high numbers. More than 200 countries tend to maintain the high-risk character- strains of lactobacilli were investigated in order to istics, whereas the offspring acquire a risk closer to select strains exhibiting high lactic acid production, that of the host countries. Low socioeconomic efficient detachment of the H. pylori, and strong status is also shown to be associated with high risk. resistance to gastric acidity. The evidence that diets high in vegetables and Lactobacillus gasseri strain OLL 2716 (LG21) fruits protect against stomach cancer is convincing. was selected for further studies in 5-week-old Summarised evidence suggests that raw vegetables gerbils. H.