Probiotic Supplements Ease Diarrhea and Other Gastrointestinal Disorders
Charlotte A. Kenreigh, PharmD; Linda Timm Wagner, PharmD

Study Summary
Probiotics are microorganisms found naturally in foods that stimulate the growth of beneficial organisms within the gastrointestinal (GI) tract. Recently, they have received increased attention in the news media. In healthy individuals, the GI tract houses more than 400 species of bacteria that are responsible for keeping harmful bacteria in check and keeping the GI tract healthy. Under certain circumstances, the balance of the bacteria within the GI tract is upset and there may be a reduction in the amount of beneficial GI bacteria. Antibiotic use, chronic diarrhea, and constipation have all been linked to this imbalance.

Early studies of antibiotic-induced diarrhea suggested that yogurt (live and active cultures) containing probiotics could help prevent and/or reduce symptoms by changing the bacterial environment of the GI tract. More recently, probiotic dietary supplements intended to promote the health of the GI tract have been introduced to the market.

Thomsen reviews the background on the use of probiotics and healthy gut flora. He offers a concise review of the available data regarding the use of probiotics in several conditions: intestinal dysbiosis, irritable bowel syndrome, inflammatory bowel disease, pouchitis, diarrhea (antibiotic-induced, travelers', acute, or infantile diarrhea), constipation, Helicobacter pylori infection, food allergies, eczema, immune modulation, hypercholesterolemia, and urogenital infections.

The author concludes that the results of clinical studies support the use of probiotics for infective, antibiotic-induced, and travelers' diarrhea; vaginal thrush and recurrent cystitis; irritable bowel syndrome; colitis; food allergies; and lactose malabsorption. Probiotics may also be useful for the prevention of pouchitis, postoperative infections, and eczema. The author does warn that probiotics should be avoided in patients who are sensitive to any component of a probiotic formulation. Additionally, he acknowledges that the labeling of many probiotic products is substandard.

Viewpoint
Consumers are frequently receiving messages through the media promoting the use of probiotics for the maintenance of GI health. This article offers important insight into the potential uses for these products. In general, probiotics are considered safe and have not been shown to interact negatively with prescription medications. However, as with any dietary supplement or natural product, the manufacture of these products may not be standardized and the purity of products cannot be guaranteed. The products can vary significantly in nature and cost.

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Boost Baby's Immune System and Aids in the Prevention and Treatment of Allergic Disease
Samuli Rautava and Erika Isolauri Department of Paediatrics, University of Turku, Finland

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system. There is accumulating evidence indicating that there is an intimate interaction between gut microbiota and host defense mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa.

Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate anti-inflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.

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Probiotics May Improve Children Health and Fight Disease
M.J. Friedrich and S. Gorback MD Department of Medicine Tufts University Boston USA

The observation that adding certain microorganisms to the diet can improve microbial functioning and benefit health has led to the concept of Probiotic therapy. Such an approach is not new. Sherwood Gorbach MD of Tufts University School of Medicine (USA) pointed out at the World Congress on Pediatric Gastroenterology, Hepatology and Nutrition in August, the study of probiotics began with Russian microbiologist, Elie Metchnikoff almost a century ago. And for thousands of years prior to Metchnikoff work, people consumed yogurts and fermented milk for their health.

In the last decade, interest in these potentially beneficial microorganisms has increased. A number of replicable, well controlled trials have been published that demonstrate the potential uses of probiotics therapy, with Bifidumbacterium and Lactobacillus for by far the best studied of these probiotic agents, said Jose Saavvedra MD of John Hopkins Medical Centre.

GUT REACTIONS
"In terms of demonstrated effects, it's clear that if you ingest any live bacteria that produce lactase you can improve lactose malabsorption," said Saavedra. Aside from this one, however, there are a number of other therapeutic applications for which certain probiotics show promise. Of particular note, he said, is the use of Bifidobacterium and Lactobacillus in the prevention and treatment of diarrhea in children.

Lactobacillus has been shown in a number of studies to decrease the duration and severity of episodes of acute diarrhea, particularly in cases caused by rotavirus, said Saavedra.

One of the largest of these is a multi center European trial involving 287 children with acute diarrhea of rotaviral origin (J Pediatr, Gastroenterol Nutr. 2000;30:54-60). In this study, children with diarrhea who were randomly assigned to receive an oral re hydration solution containing a live preparation of Lactobacillus GG (LGG) showed a significant reduction in the duration of disease and in hospital stays compared with children who received the re hydration solution with placebo.

Saavedra, said another potential use for probiotics is to counteract episodes of diarrhea that can occur with antibiotics. In one placebo-controlled study (J Pedeatri. 1999;135:564-568), LGG was co administered with antibiotics to children treated for minor bacterial infections, resulting in a reduction in the severity and incidence of diarrhea in the children receiving the probiotic.

EFFECTS BEYOND GUT
Probiotics also may be useful in ameliorating some allergic reactions. Tufts' Gorbach discussed evidence from a controlled study showing that infants with atopic dermatitis and challenge-proven milk allergy who received formula supplemented with LGG had significant improvement in the severity of their eczema compared with children who did not receive LGG (J Allergy Clin Immunol. 1997;99:179-185).

Commenting on the study, Gorbach said, "Here's an example of a food allergy reflected in the skin by eczema, which is improved by administration of healthy bacteria." He added that LGG may help ameliorate the allergic reaction by restoring intestinal permeability which is disrupted in children with food allergy.

Although there are fewer studies in this area, probiotics also may be useful in treating respiratory infections in children. Gorbach described a recent unpublished report from Helsinki in which 571 children in 18 day care centers received milk containing LGG or a placebo. A significant reduction in respiratory infections, including sinusitis, bronchitis, and pneumonia, was seen in the children taking LGG, he said. There was also a reduction in the amount of antibiotics administered to these children by the physicians.

It seems, then, said Gorbach, that two mucosal surfaces, the gastrointestinal tract and the respiratory tract, may be benefited and protected by oral administration of a probiotic. How bacteria may improve intestinal and systemic conditions is not entirely clear, but clues to possible mechanisms are emerging.

There is also evidence that probiotics can induce expression of mucin proteins, the large glycoproteins secreted by epithelial cells in the intestinal tract that provide protection from bacteria and viruses, said David Mack, MD, of Nebraska Medical Center, Omaha, who presented evidence for this mechanism at the meeting. He and his colleagues have shown that certain lactobacilli strains can increase the expression of MUC3 messenger RNA expression and MUC3 protein translation in cell culture and also inhibit adherence of enteropathogenic Escherichia coli to intestinal mucosal cells in culture. They hypothesize that by inducing mucin gene expression, probiotic agents may be able to minimize the interaction of other microbes with intestinal mucosal cells and lessen intestinal inflammation.

THE ROAD AHEAD
Preliminary data suggest that there are a number of other conditions in children for which probiotics may prove useful, said Johns Hopkins' Saavedra. These include inflammatory disorders of the gastrointestinal tract, such as inflammatory bowel disease and necrotizing enterocolitis. Treatment of hypercholesterolemia also has been reported, but there have been no major studies. And if immunoenhancing effects can be definitively demonstrated in humans, he said, probiotics could be used to reduce vaccine doses.

Other important areas of study include colon carcinogenesis. Because a number of changes in the intestinal medium can lead to a decrease in concentration of potential carcinogens, probiotics may be useful in cancer prevention, said Saavedra.

Are probiotics safe? Saavedra said that many reports and the fact that for centuries people have ingested fermented milk products with apparently no ill effects seem to indicate that these agents are safe. He stressed that more research needs to be done to standardize and regulate "what benefits we're getting from what strain and at what dose" for the full clinical potential of probiotics to be realized.

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The FIRST STEP to a Strong Immune System
Dr Debby Hansen Director of The Edison Institute of Nutrition, Federickton, New Brunswick, Canada

We all know we need a strong immune system in order to ward off pathogens so we don't get sick. But how many know that there is a very close relationship between the immune system and the intestinal tract. If we are to support immune function, we must start by supporting digestion, assimilation and elimination.

We have all heard the expression, "You are what you eat". Actually you are what you eat and assimilate. But it is equally true that you are what you do not eliminate. If undigested food and waste products are not eliminated from the body they accumulate, putrefy, feed unfriendly bacteria, and become reabsorbed. Every tissue and organ of the body will feel the effects of these toxic substances. This is the underlying cause of the majority of today's diseases and ill health

The Gastrointestinal Immune Connection
The gastrointestional (GI) tract is the major center of immune response. Gut Associated lymphoid Tissue (GALT) is the largest lymphoid organ in the body. The small intestine contains 80% of the immune-producing cells in the body.

There are 400-500 indigenous species of micro flora in the large intestine, many of which are unculturable and therefore virtually unknown. There are 100,000 billion viable bacteria in the GI tract. Bacteria should compose 33% to 50% of fecal matter. Normal bowel flora is essential to the immune system, starting from birth. Two of the most studied beneficial bacteria are strains of Lactobacilli and Bifidobacteria.

When there are balanced numbers of micro flora, it takes 100,000 Salmonella enteritidis organisms to cause disease (food poisoning). Although antibiotics can save lives, they can also destroy beneficial bacteria, suppress immune function, cause serious intestinal symptoms, stress the liver and kidneys, deplete beneficial vitamins and minerals, and cause other side effects.

Pathology
Constipation creates a disurbance of intestinal bacteria. Dangerous toxins are produced and absorbed, increasing the workload of all excretory organs. Intestinal constipation causes cellular constipation. Cells, tissues and organs cannot reproduce, repair, and eliminate wastes efficiently. Functional disturbance can occur in any organ system resulting in degenerative and chronic illness.

The most common cause of constipation are a low-fibre, low-nutrient diet, insufficient fluid intake, lack of exercise, drugs, a low functioning thyroid, low stomach hydrochloric acid production, and ignoring the urge to eliminate.

Diarrhea is frequent liquid stools. The most common causes are viral or bacterial infection, food allergies/intolerances, parasites and antibiotics. Loose and frothy stools may indicate intestinal malabsorption. Mucus in the stool may indicate irritation and possible intestinal damage.

Bowel Transit Time
Constipation is thought by many to mean infrequent bowel movements that are hard, dry and difficult to pass stools. Contrary to this belief, they may actually be formed and normal in appearance. Ideally we should have a bowel movement shortly after each major meal or three times a day. However, even this is not always an indicator of healthy bowel function. Transit time through the bowel is also important. We should eliminate the residue of each meal is 18-24 hours. In many cases, it is not eliminated for many days afterward.

Many people have the misconception that it doesn't matter how often you have a bowel movement as long as it is "regular". This belief has led many to conclude that as little as one or two bowel movements a week is "normal". It may be "normal" in the sense that it is "common" but it definitely is not healthy. In fact it causes "autointoxication", being poisoned by substances produced within the body. Others have the opposite mistaken belief that if they have two to three bowel movements a day, that they have diarrhea.

Do most people know when they are constipated? Dr. Bernard Jensen, a renowned authority on bowel health, reports on 300 autopsies performed at the National College in Chicago. Health histories revealed that only 15 reported being constipated and some reported as many as 5-6 bowel movements a day. What did the results reveal? Only 15 were not constipated while the other 285 were. The bowel walls were encrusted with material (in once case peanuts) that had obviously been there a very long time. Some had bowels that were 12 inches in diameter. Any wonder why drug stores are full of breath fresheners and deodorants? The outside is a true reflection of the inside.

Nutritional Support

• The bowel functions best when there is sufficient water (6-8 glasses a day)
• High fibre foods such as fresh fruits, vegetables, berries, raw nuts and seeds, legumes, and whole grains provide fibre and the nutrients for healthy bowel function and repair
• Live culture ferment foods (yoghurt, kefir, sauerkraut) supply friendly bacteria for the bowel. Probiotics (acidophillus and bifidus strains) can be taken in supplement form to repopulate the bowel with friendly bacteria. This is especially important after antibiotics use and for those who are allergic or intolerant to diary products
• Avoid refined sugar, refined flour, food additives and chemicals, alcohol, and smoking, all of which affect intestinal micro flora
• Fresh ground flax seeds and hemmp hearts are excellent ways to add extra fibre and essential fatty acids. Psyllium provides extra fibre and absorbs harmful toxins. Be sure to drink plenty of water
• Digestive enzymes increase digestion, allowing nutrients to be absorbed, and reduce toxic by-products of poor digestion
• Ginger, chanomile, and peppermint teas are especially good for the GI tract, improving digestion, and promoting healthy function.

The best approach for those wanting to strengthen their immune system is to support digestion, assimilation and elimination with an individual program. Holistic Nutrition Consultants trained at the Edison Institute of Nutrition are qualified to assess diet, health history, and symphomology to create individualised programs to build healthy balanced bodies.

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Inflammatory Bowel Disease
Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) Resta-Lenert S, Barrett KE
Department of Medicine, School of Medicine, University of California-San Diego, UCSD Medical Center 8414, 200 West Arbor Drive, San Diego, CA 92103, USA. srestalenert@ucsd.edu

BACKGROUND
The colonic epithelium maintains a life long reciprocally beneficial interaction with the colonic microbiota. Disruption is associated with mucosal injury.

sAIMS
We hypothesised that probiotics may limit epithelial damage induced by enteroinvasive pathogens, and promote restitution.

METHODS
Human intestinal epithelial cell lines (HT29/cl.19A and Caco-2) were exposed to enteroinvasive Escherichia coli (EIEC 029:NM), and/or probiotics (Streptococcus thermophilus (ST), ATCC19258, and Lactobacillus acidophilus (LA), ATCC4356). Infected cells and controls were assessed for transepithelial resistance, chloride secretory responses, alterations in cytoskeletal and tight junctional proteins, and responses to epidermal growth factor (EGF) stimulation.

RESULTS
Exposure of cell monolayers to live ST/LA, but not to heat inactivated ST/LA, significantly limited adhesion, invasion, and physiological dysfunction induced by EIEC. Antibiotic killed ST/LA reduced adhesion somewhat but were less effective in limiting the consequences of EIEC invasion of cell monolayers. Furthermore, live ST/LA alone increased transepithelial resistance, contrasting markedly with the fall in resistance evoked by EIEC infection, which could also be blocked by live ST/LA. The effect of ST/LA on resistance was accompanied by maintenance (actin, ZO-1) or enhancement (actinin, occludin) of cytoskeletal and tight junctional protein phosphorylation. ST/LA had no effect on chloride secretion by themselves but reversed the increase in basal secretion evoked by EIEC. EIEC also reduced the ability of EGF to activate its receptor, which was reversed by ST/LA.

CONCLUSIONS
Live ST/LA interact with intestinal epithelial cells to protect them from the deleterious effect of EIEC via mechanisms that include, but are not limited to, interference with pathogen adhesion and invasion. Probiotics likely also enhance the barrier function of naive epithelial cells not exposed to any pathogen.

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Role of Functional Foods ? Probiotics Probiotics given to pregnant and lactating mothers reduced atopic eczema during the first two years of their child's life
Luise Kalbe, PhD., Brigitte Reusens, PhD., and Professor Claude Remacle, Cellular Biology Laboratory, University de Louvain, Belgium

Nutrition is truly functional during pregnancy and lactation, because it exerts prenatal and early postnatal influences on the developing baby: maternal nutrition affects the intra-uterine development of the baby and determines the quality of the breast milk needed to support adequate growth and gut-flora composition.

The more commonly used approach to functional foods involves designed foods in which ingredients have been added or removed. Only the former category will be considered here. Different types of designed foods are classified as functional foods: pre-biotics and probiotics, vitamins and minerals, bioactive molecules, and fatty acids.

Probiotics added to food products must meet several criteria such as a beneficial effect on health, survival during transit through the gastrointestinal tract, adhesion (permanent or temporarily) to the intestinal epithelial cell lining, production of antimicrobial substances toward pathogens or stabilisation of the intestinal microflora. Over-the-counter supplements, however, may not fulfill these criteria and may not even survive in the gastrointestinal tract.

With particular relevance for the subject on hand are several trials with either pregnant women, lactating mothers and their babies, or with children, that have demonstrated several beneficial effects of probiotics. These include the maturation and health of the intestinal tract and the immune system, the reduction of lactose intolerance and allergy prevalence, the reduction of the risk of microorganism-induced diarrhea, or the enhancement of nutrient bioavailability.

Not only are probiotics therefore promising functional foods for pregnant women and infants, but they can be considered for prophylactic as well as therapeutic uses. Prophylactic use of probiotics for women during the last trimester of pregnancy and through childbirth, for instance, permanently colonised the gastrointestinal tracts of their infants. It is not yet known whether the immune-boosting properties of these probiotics require periodic pulse dosage or continuous administration.

Probiotics given to pregnant and lactating mothers increased the immuno-protective potential of breast milk and reduced the incidence of atopic eczema during the first two years of life in their children.

Another study showed that in addition to allergy occurrence, the number of infections and the need for antibiotics due to preventive probiotic treatment after birth were reduced even ten years later.

Preventive feeding of fermented milk also increased the absorption of iron due to the liberation of lactic acid and other organic acids during fermentation. The authors even suggested that consumption of fermented milk during meals might also have a positive effect on the absorption of iron from other foods. Based on such findings and the fact that even temporary colonisation of a baby's intestines with probiotic bacteria prevents colonisation with less beneficial bacteria, probiotic supplementation of milk formula has been proposed.

Probiotic foods are non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon. Prebiotic oligosaccharides from different origins have been used as ingredients in functional foods. They may be inulin; lactulose; fructo-, galacto-, isomalto- or xylo-oligosaccharides.

According to their chemical nature they support higher populations of individual bacteria species in the gut flora. The largest increase in lactobacilli was seen with xylo-oligosaccharides and lactulose. Although fructo-oligosaccharides promoted a large increase in lactobacilli, they also supported higher populations of streptococci than did galacto-oligosaccharides. The latter supported higher populations of bifidobacteria and higher levels of lactate than fructo-oligosaccharides. Latulose and xylo- and galacto-oligosaccharides thus stimulate the growth of bacteria found in the colon of breast-fed infants, on the other hand, have a more diverse and adult microflora and tend to suffer more from microbial infections than breast-fed infants.

This means that lactulose, xylo- and glacto-oligosaccharides are the prebiotic oligosaccharides of choice for functional foods aimed at infants. Supplementing milk formula with these oligosaccharides should therefore circumvent the problem of aberrant colon colonisation in formula-fed infants. However, prebiotics functional foods will be effective only where there is a real need, since responses to prebiotics depend on the numbers of bacteria colonising the colon. Individuals with low bifidobacterial counts displayed much higher responses to prebiotics than individuals with higher bacterial counts.

Prebiotics positively affect the absorption of various minerals as well as mineral contents in bones. The risk of osteoporosis is higher in formula-fed children than in breast-fed children born at term, even though milk formula has a higher calcium content than breast milk. Prebiotic supplementation of milk formula might thus help reduce the risk of osteoporosis in formula-fed children born at term.

This finding does not apply, however, to children born pre-term, where the source of milk does not seem to influence bone mass later on. Nevertheless, it might be worthwhile later on to follow these term and pre-term children into adult age to check for possible long-term protection against osteoporosis due to early prebiotic supplementation.

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Bacteria hope for Asthma
Lancet as reported The Age, Melbourne, Australia

Treating pregnant women with "good bacteria" will pevent thousands of children contracting asthma by strengthening the baby's fledgling immune system, a new study shows.

Lactobacillus, the "good bacteria", can be found in yoghurt and other diary products, and is a normal ingredient in a healthy stomach.

They study, published in Lancet, found additional amounts of Lactobacillus would cause a child's immune system to mature at an advanced rate. A bady normally builds up an immune system within the first few months of its life, a slow process that eventually strengthens the immune system to allergies.

By age seven, 6 percent of the children had been diagnosed with asthma. Doctors now believe it is best to act before the child is born by medicating the unborn child's mother with "good bacteria" to stimulate the child's immune system.

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Antifungal Effect of Lactic Acid Bacteria
L. Vanne, T. Kleemola, A. Haikara VTT Biotechnology

AIM
In this study, the possible antifungal effects of lactic acid bacteria against toxigenic Penicillium and Aspergillus strains were screened in vitro. The work is a part of the EU project "Prevention of ochratoxin A in cereals". (QLK1.-CT-1999-00433).

MATERIALS AND METHODS
The mould strains selected for this study were 15 identified Penicillium verrucosum and four Asperillus ochraceus isolated from wheat and barley. The inhibition of mould growth was screened with seven lactic acid bacteria (LAB), partly based on earlier studies of their anti fungal effects

A summary of LAB used in this study is presented below:

The preliminary screening of the anti fungal effect of the LAB was carried out by automated turbidometry.

RESULTS
The anti funal effect measured by automated turbidometry varied between 20 and 55%. The set inhibition level of 40% was achieved in 22 of 104 combinations of LAB and P. verrucosum. The three most effective LAB strains were Lactobacillus plantarum E76, L. plantarum E98 and L. amylovorus E576. The inhibition of A. ochraceus by LAB was found to be more than 40% in 11 out of 26 combinations. The inhibition caused by LAB is a combined effect of lactic acid and anti-microbial substances produced by the bacteria. All the four LAB strains studied using the indirect impedimetric method were able to delay or even inhibit the growth of A. ochraceus and P. verruosum during the 90-hour monitoring period. The most effective strains L. plantarum E76 and L. amylovorus E576, were able to inhibit the growth of all 14 fungal strains tested.

CONCLUSION AND FUTURE PLANS
The results achieved in this study show clearly that the growth of toxigenic storage fungi can be restricted by LAB in vitro. Further studies with irradiated barley as growth substrate are going to show the potential of the technique in barley storage and processing.

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Probiotics help in nasal congestion
American Journal of Clinical Nutrition, Vol. 77, No. 2, 517-520, February 2003

Dietary supplements
Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and ß-hemolytic streptococci) 1,2,3 Ulrich Glück and Jan-Olaf Gebbers 1 From the Suva, Swiss National Accident Insurance Institute, Division of Occupational Medicine, Lucerne, Switzerland (UG), and the lnstitute of Pathology and Environmental Medicine, Kantonsspital Luzern, Lucerne, Switzerland (J-OG).

Background
As a bacterial reservoir, the nose may harbor potentially pathogenic bacteria (PPB: Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococci, and Haemophilus influenzae). In patients carrying PPB, antiseptic regimens could be crucial for infection control after major operations on or injuries of the head, nasal sinuses, or lungs. Such regimens may also be important for diabetic patients and persons receiving hemodialysis, in intensive care units, or with impaired immunity due to various other causes.

Objective
We tested a possible effect of the ingestion of probiotics on the bacterial flora of the nose.

Design
In an open, prospective trial, 209 volunteers were randomly assigned to consume either a probiotic, fermented milk drink [65 mL with Lactobacillus GG (ATCC 53103), Bifidobacterium sp B420, Lactobacillus acidophilus 145, and Streptococcus thermophilus; n = 108] or standard yogurt (180 g; n = 101) daily for 3 wk. Nasal microbial flora were analyzed on days 1, 21, and 28. The microbial examination was blinded to the source of the samples.

Results
We found a significant reduction (19%; P < 0.001) in the occurrence of nasal PPB in the group who consumed the probiotic drink but not in the group who consumed yogurt. The effect was mainly on gram-positive bacteria, which decreased significantly (P < 0.05).

Conclusions
The results indicate that regular intake of probiotics can reduce PPB in the upper respiratory tract. The results also indicate a linkage of the lymphoid tissue between the gut and the upper respiratory tract.

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