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Table of Contents

image Probiotics
image Intestinal microflora and antibiotic therapy
image Inability of lactobacillus casei strain GG, L. acidophilus, and bifidobacterium bifidum to degrade intestinal mucus glycoproteins
image Use of lactobacilli in gastroenterology
image Antibiotics and intestinal flora
image Does nutritional therapy in inflammatory bowel disease have a primary or an adjunctive role?
image The faecal flora of patients with Crohn's disease
image Intestinal immunocompetency and/or cancer control
image Viability and dose-response studies on the effects of the immunoenhancing lactic acid bacterium Lactobacillus rhamnosus in mice.
image Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies?
image Clinical applications of probiotic agents.
image Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.



Szajewska H.; Albrecht P. Dr. H. Szajewska, Klin. Gastroenterol./Zyw. Dzieci, Akademia Medyczna, ul. Dzialdowska 1, 00?184 Warszawa Poland

Pediatria Polska (Poland), 1997, 72/6 (535?539)
This paper presents current views on probiotics. Their potential mechanism of action and use in the prevention and treatment of gastrointestinal diseases are discussed.

Intestinal microflora and antibiotic therapy

Socha J. Oddzial Gastroenterologii, Centrum Zdrowia Dziecka, Al. Dzieci Polskich 20, 04?736 Warszawa Poland

Pediatria Polska (Poland), 1995, 70/7 (547?552)
Antibiotic therapy is one of the major factors leading to disturbances in the intestinal fora. This can lead to chronic diarrhea and life threatening pseudomembranous colitis. Much attention had recently been focused on so?called translocation of endotoxins and bacteria through the intestinal wall which leads to systemic infection, shock and multiorgan failure. Prevention is based on the proper choice of antibiotic and administration of lactic?acid bacteria.

Inability of lactobacillus casei strain GG, L. acidophilus, and bifidobacterium bifidum to degrade intestinal mucus glycoproteins

Ruseler?Van Embden; Van Lieshout L.M.C.; Gosselink M.J.; Marteau P. Department of Immunology, Erasmus University, Dr. Molenwaterplein 50, 3015 GE Rotterdam Netherlands

Scandinavian Journal of Gastroenterology (Norway), 1995, 30/7 (675?680)
Background: Lactic acid bacteria have been suggested for use in the prevention of relapse of ulcerative colitis and of recurrent pouchitis. These strains may not damage the protective intestinal mucus glycoproteins. Methods: Lactobacillis casei strain GG and strains isolated from a commercial fermented product (Lactobacillus acidophilus, Bifidobacterium bifidum, and a mesophylic lactic culture) were cultured in vitro on hog gastric mucin and human intestinal glycoproteins. Furthermore, germ?free rats were mono?associated with Lactobacillus GG and poly?associated with the other strains. Glycoproteins were isolated from rat distal ileum, cecum, and colon. Mucus degradation was established by assaying carbohydrates (hexosamines, hexoses, pentoses), proteins, and blood group antigenicity. Results: All strains colonized the intestinal mucus but were not found in the deep crypts. Degradation of mucus glycoproteins was observed neither in vitro nor in vivo. Conclusion: The tested strains do not break down intestinal mucus glycoproteins and thus far are safe to use for therapy.

Use of lactobacilli in gastroenterology

Kocian J.; Synek P. Videnska 800, 140 59 Praha 4 Czech Republic

In a clinical trial the authors tested the preparation Lactobacillus acidophilus of Rosell Co., Canada containing 2 billion lyophilized bacteria per capsule in 55 patients with dyspepsia caused by dysbiosis of the digestive tract. The best and most rapid results were achieved in patients with dysbacteriosis which developed as a result of administration of broad spectrum antibiotics; the preparation also exerted a favourable effect in postirradiation colitis. Within one week very distressing bloating in biliary dyspepsia receded and the preparation proved also very useful in patients with blind loop syndrome or with a digestive tract colonized by pathogenic strains due to reduced protection (impaired gastric acid secretion, motility). The preparation was ineffective in two patients with a biliodigestive fistula and in patients with M. Crohn without complicating stenosis and prestenotic dilatation. In 2 patients with associated lactose intolerance the use of lactobacilli increased lactose tolerance, mainly from milk, cream cheese and less from cheese. The highest Ca intake in patients was, however, from cheese, followed by milk and the least by cream cheese.

Antibiotics and intestinal flora

ANTIBIOTIKA UND DARMBAKTERIEN Reichlin B.; Gyr K. Abt. Gastroenterol., Dept. Inn. Med., Univ. Basel SWITZERLAND

THER. UMSCH. (SWITZERLAND), 1980, 37/3 (194?197)
There are many interactions between antibiotics and the intestinal microflora. The purpose of this review is to focus above all on four such interactions with some clinical importance: General side?effects of antibiotics on the gastrointestinal tract are described briefly, problems of antibiotic resistance in intestinal bacteria and the new understanding of pseudomembranous colitis are explained in more detail. Finally some aspects of colonisation of the gastrointestinal tract with Lactobacillus acidus are discussed.

Does nutritional therapy in inflammatory bowel disease have a primary or an adjunctive role?

O'Morain C.A. Department of Gastroenterology, Meath/Adelaide Hospitals, Peter Street, Dublin 8 Ireland

SCAND. J. GASTROENTEROL. SUPPL. (Norway), 1990, 25/172 (29?34)
The aetiology of inflammatory bowel disease (IBD) remains unknown, and many methods of treatment have been advocated. Patients with IBD are often nutritionally deficient and in negative nitrogen balance. The cause is multifactorial and includes decreased intake and absorption due to previous resection or mucosal involvement or increased exudation. General recommendations of vitamin and mineral supplements are usually made for these patients. Diet may have a more fundamental role in the aetiology and treatment of Crohn's disease, although this is not certain. Several controlled studies have confirmed that an elemental diet is as effective as steroids in inducing a remission in patients with acute Crohn's disease. Bacteria have also been implicated in the aetiology of Crohn's disease. Dietary measures may alter the intestinal flora and could result in a decrease of toxin production, which has been shown to correlate with clinical improvement. Although elemental diets are not effective in the treatment of ulcerative colitis, dietary measures may still be important. Preliminary studies suggest that eicosapentaenoic acid, which inhibits the production of mediators of inflammation by competing with enzymes in the arachidonic acid pathway, may be effective. Recent findings of increased faecal bile acids in patients with long?standing ulcerative colitis who developed dysplasia or carcinoma suggest that dietary measures may counteract these developments. It does appear that nutritional therapy in patients with IBD has both a primary and adjunctive role.

The faecal flora of patients with Crohn's disease

Wensinck F.; Custers?Van Lieshout L.M.C.; Poppelaars?Kustermans P.A.J.; Schroder A.M. Dept. Med. Microbiol., Erasmus Univ., Rotterdam NETHERLANDS

J. HYG. (ENGLAND), 1981, 87/1 (1?12)
The faecal flora of patients with Crohn's disease was compared with that of healthy subjects. In patients with terminal ileitis, numbers of anaerobic gram?negative and coccoid rods (species of Eubacterium and Peptostreptococcus) were higher than in the controls whereas anaerobic gram?positive rods and cocci and aerobes occurred in normal numbers. The composition of the flora was neither influenced by duration of the disease nor by ileocaecal resection. In healthy subjects and patients, a chemically defined diet induced only slight changes in the flora. Thus, the flora in terminal ileitis although stable was permanently abnormal. In patients with Crohn's colitis, abnormally low numbers of anaerobes were found in patients with severe, bloody diarrhoea while aerobic counts were normal. The flora in patients with mild colitis was similar to that in terminal ileitis. It is suggested that the abnormal flora composition might be an expression of the genetic predisposition to Crohn's disease.

Intestinal immunocompetency and/or cancer control

Res Commun Chem Pathol Pharmacol 1994 Apr;84(1):111-8

The conditions and diseases that have become more prevalent are almost wholly of environmental origin. The most plausible contributory factor is diet. In diet, calorie intake has increased, total intake of protein has risen, and more animal but less vegetable protein is consumed. Dietary fiber is described as the proportion of plant foods not digested in the human small intestine. For the purpose of practical classification, dietary fiber is divided into 'water soluble' and 'water insoluble' types. The soluble fibers (pectins and gums) slow glucose absorption, and reduce serum cholesterol. Insoluble fibers (cellulose, hemicelluloses, and lignin) decrease intestinal transit time and increase fecal bulk, thus preventing colon cancer. Among the various kinds of pectin, apple pectin exerts a bacteriostatic action and therefore may change the composition of the intestinal flora. The diet supplemented with 20% apple pectin significantly decreased the number and the incidence of AOM?induced colon tumors in rats. Fecal beta?glucuronidase activity was significantly lower in the group fed pectin. The prostaglandin E2 (PGE2) level in the distal colonic mucosa and blood of portal vein was lower in rats fed 20% pectin than those fed the basal diet. The ability of apple pectin to decrease PGE2 was dose?dependent, and those results suggest an anti?inflammatory effect in the bowel. Rats fed apple pectin showed a significantly lower incidence of hepatic metastasis than those fed the basal diet. To determine whether the anti?inflammatory effect of Lactobacillus on the hepatic metastasis model was the same as apple pectin, Lactobacillus casei was selected. Metastatic nodules were significantly reduced, especially in the group receiving pretreatment. The suppression of colonic carcinogenesis in AOM induced colon tumors in rats was evident with three kinds of living bacterial mixture (S. faecalis, B. mesentericus, C. butyricum). In conclusion, apple pectin has a scavenger effect in the intestinal digestion and portal circulation system as an anti?inflammatory food. Dietary fibers like pectin, and Lactobacillus have a very important function in the intestinal tract as anti?inflammatory foods.

Viability and dose-response studies on the effects of the immunoenhancing lactic acid bacterium Lactobacillus rhamnosus in mice.

Gill HS, Rutherfurd KJ. Milk and Health Research Centre, Institute of Food, Nutrition and Human Health,
Massey University, Palmerston North, New Zealand.

Br J Nutr 2001 Aug;86(2):285-289

Previous studies have indicated that the lactic acid bacterium Lactobacillus rhamnosus HN001 can enhance immune function in mice, following oral delivery. However, the influence of bacterial cell viability on immunoenhancement, and the optimum dose of HN001 required for this effect, have not been determined. In the present study, both live and heat-killed preparations of L. rhamnosus HN001 were shown to enhance the phagocytic activity of blood and peritoneal leucocytes in mice, at a dose of 109 micro-organisms daily. In contrast, only live HN001 enhanced gut mucosal antibody responses to cholera toxin vaccine. Feeding mice with 107 viable HN001/d for 14 d was shown to enhance the phagocytic capacity of blood leucocytes, with incremental enhancement observed at 109 and 1011 daily doses. In contrast, a minimum dose of 109 viable HN001/d was required to enhance the phagocytic activity of peritoneal leucocytes, and no further increment was observed with 1011 daily. This study demonstrates that L. rhamnosus HN001 exhibits dose-dependent effects on the phagocytic defence system of mice, and suggests that while the innate cellular immune system is responsive to killed forms of food-borne bacteria, specific gut mucosal immunity may only be stimulated by live forms.

Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies?

Cross ML, Gill HS. Milk & Health Research Centre, Institute of Food, Nutrition and Human Health,
Massey University, Palmerston North, New Zealand.

Int Arch Allergy Immunol 2001 Jun;125(2):112-119

Studies in gnotobiotic animals have suggested that the intestinal bacterial flora may play an important role in priming the immune system during ontogeny to limit dysfunctional responses, including allergy. Prospective clinical studies have identified a higher incidence of allergy expression in early childhood among children who have low enteric populations of lactic acid bacteria (LAB), such as lactobacilli and bifidobacteria, further supporting a role for gut-colonizing bacteria in regulating immunological atopy. There is some evidence to suggest that supplementing the human diet with probiotic LAB might combat both allergy development and expression of atopy in allergy sufferers; however, definitive information, in the form of controlled intervention trials, remains scant. Recent immunological evidence has indicated that certain strains of LAB can stimulate the production of type I and II interferons and pro-interferon monokines (IL-12 and IL-18), following contact with the immune system; therefore, probiotic forms of immunoregulatory LAB could be used as dietary supplements to modify the gut microflora and provide pro-T helper cell 1 (Th1) STAT-activating signals sufficient to deviate the immune phenotype and correct the Th2-type bias which promotes allergy. This review outlines the clinical and laboratory evidence of a role for LAB in combating allergies, and attempts to explain this phenomenon in terms of our current understanding of immunoregulatory signals produced by gut-colonizing microbes. Copyright 2001 S. Karger AG, Basel

Clinical applications of probiotic agents.

Saavedra JM. Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Am J Clin Nutr 2001 Jun;73(6):1147S-1151S

In the past century the beneficial roles of nonpathogenic bacteria in the intestinal lumen were described. In the past decade there has been a dramatic increase in scientific work supporting the concept that there are clinical benefits to ingesting specific nonpathogenic organisms (probiotics). The potential benefits of modifying the intestinal flora composition of certain high-risk groups, eg, premature infants, travelers, and children receiving antibiotics, are emerging in the literature. Studies documenting prophylactic and therapeutic benefits in acute viral gastroenteritis and in atopic disease point not only to the potential applications, but also to the fact that the mechanisms of action of these agents may be due to their interaction with the gut as an immunologic organ. The benefits documented thus far are of varying degree and are most likely dependent on the number of agents, the dose, the dosing patterns, and the characteristics of the host and its underlying luminal microbial environment. Consequently, the safety and specification of a particular probiotic agent and methods of delivery to a particular population for a particular purpose should be carefully documented before making broad recommendations. The cost-benefit assessment of adding probiotics to our diet for prophylactic or therapeutic purposes, as well as better regulation of these agents as commercial products, is also needed.

Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.

Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E.
Department of Paediatrics, University of Turku and Turku University Hospital,

Lancet 2001 Apr 7;357(9262):1076-1079

BACKGROUND: Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy). METHODS: In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint. FINDINGS: Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6). INTERPRETATIONS: Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.