© Borgis - New Medicine 1/2006, s. 3-6
Elżbieta Trafalska, Andrzej Grzybowski
Probiotics and prebiotics in prevention of chronic civilization diseases
Nutrition, Hygiene and Epidemiology Unit, Department of Hygiene and Epidemiology, Medical University of Łódź, Łódź, Poland
Head of Department: Professor Andrzej Grzybowski MD, PhD
Summary
SUMMARY
Gastrointestinal microflora modification through regular probiotic food intake can protect against gastrointestinal diseases and influence human health status. There are very promising reports on application of probiotics and prebiotics in health promotion in order to reduce the risk of chronic civilization diseases. Probiotics decrease the faecal enzymes of mutagenesis and carcinogenesis, have hypocholesterolemic and hypolipemic effects, increase bioavailability and calcium absorption, and improve glucose tolerance, so they diminish the risk in cancer cases, cardiovascular diseases, osteoporosis and diabetes mellitus. The natural bifidobacterial yogurts of the new generation are particularly valuable as a healthy diet supplement because of their high nutritional value and the pro- and prebiotics presence.
The quantitative and qualitative composition of the gastrointestinal microbial flora of a healthy human being is relatively stable, with the domination of beneficial bacteria (especially of the protective Lactobacillus and Bifidobacterium types). They create a natural protective barrier against pathogens. The quantitative participation of the colonic bacteria fluctuates and depends on age, physiological status, diet, medications, the host´s immune system effectiveness and other environmental factors. It can be modulated through the probiotic flora taken with food, thus creating in the gastrointestinal tract conditions conducive to the development of health-protecting bacterial strains, with the simultaneous inhibition of pathogenic flora, the improvement of intestinal epithelium functions and the modulation of immune system parameters [1, 2, 3].
Dietary modulations of the human gut microflora can be of great benefit to health. The most frequently used dietary method of influencing the gut flora composition is the consumption of probiotic food [1, 4, 5].
This kind of functional food could contain probiotics (specific live microorganisms that have a beneficial effect on the host) or prebiotics (specific non-digestible carbohydrates such as inulin, oligofructose and oligosaccharides, non-absorbable in the small intestine, which favourably affect the host through selective stimulation of growth and activity of selected colonic microorganisms) or be a mixture of pro- and prebiotics (called synbiotics). In the group of functional food products containing probiotic bacteria, fermented dairy products are the most common [6, 7].
The principal effect of probiotics is characterized by stabilization of the gut microflora. The clinical benefit of probiotics was shown when used to treat conditions in which the gut microbiology is disturbed by changes in the environment (traveller´s diarrhoea) or by adding antimicrobial therapy (antibiotic-associated diarrhoea). The best documented clinical application of probiotics is in the treatment of acute diarrhoea caused by rotavirus infection especially in infants. The beneficial role of probiotics in secondary lactose intolerance in adults is also well known [8, 9, 10, 11].
The ingestion of probiotic bacteria can potentially stabilize the immunologic barrier in the gut mucosa by reducing the generation of local proinflammatory cytokines, which can be observed in inflammatory bowel diseases, food allergy and atopic eczema [8, 12, 13, 14].
Functional dairy products may be used not only to enhance a certain physiological function, but also to reduce the risk of disease. These food products have a significant role in reducing the risk of chronic civilization diseases, e.g. cancer, cardiovascular diseases, osteoporosis and osteopenia, glucose intolerance and diabetes mellitus.
Cancer
Epidemiological evidence suggests a negative correlation between incidence of certain cancers, including colon cancer, and intake of fermented dairy products. The mechanisms by which lactic acid bacteria may have an effect on colon carcinogenesis is certainly unknown. Some of the mechanisms that may be involved include enhancement of the host´s gut immune response, suppression of harmful intestinal bacteria, reduction of pH concentration in the colon, reduction of faecal enzymes converting procarcinogens to carcinogens, production of antimutagenic compounds or sequestration of potential mutagens.
Probiotics may stimulate both the non-specific and the specific immune systems, e.g. by increasing IgA secretion or various cytokines induction. They may also enhance the post-immune response.
Probiotics may alter the metabolism of intestinal flora, and may produce antitumour factors. There have been studies on several lactic acid bacteria of the human colon, especially Bifidobacterium longum, that show that this organism may reduce tumour ornithine decarboxylase activity and have strong antitumour activity [15].
Elevated activity of several bacterial faecal enzymes, some of which are involved in the metabolism of genotoxic nitrates, is associated with an increased risk of colon cancer. The activity of these enzymes can be altered by diet or antibiotic intake. Lactobacillus acidophilus and Lactobacillus gasseri were shown to reduce the faecal enzyme activity of nitroreductase, azoreductase and b-gucuronidase in humans, with a reduction by 50% or 75% in the activities of these enzymes during a period of Lactobacilli feeding [16, 17].
Wollowski et al. investigated the protective effect of several strains of lactic acid bacteria against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. Oral treatment with Lactobacillus bulgaricus protected against DMH-induced DNA damage in the colon. It is speculated that products of the proteolytic activity of Lactobacillus may have produced the effect [18].
Not only probiotics but also prebiotics may have potential health implications for protection against cancer. Experimental data showed that the incidence of the so-called aberrant crypt foci induced by colon carcinogens such as azoxymethane and dimethylhydrazine was reduced significantly in rats fed inulin-type fructans. A synbiotic approach combining inulin and bifidobacteria was shown to be more effective than either the probiotic or the prebiotic alone. It may be accounted for by the possible anticarcinogenic activity of butyrate. Butyrate, along with other short-chain fatty acids, is produced by bacterial fermentation of the various oligosaccharides in the colon. Some studies suggest that butyrate may induce growth arrest and cell differentiation and may also upregulate apoptosis [19, 20].
The prebiotic oligosaccharides may also aid in increasing concentrations of calcium and magnesium in the colon. Elevated concentrations of these cations may help to control the rate of cell turnover and to control the formations of insoluble bile salts of fatty acids, which might reduce the potential damaging effects of bile or fatty acids on colonocytes [18, 21].
Cardiovascular diseases
Probiotics can lower the cardiovascular disease risk through the decrease of LDL-cholesterol and increase of HDL-cholesterol level.
A double-blind placebo-controlled trial of 70 overweight people found that a probiotic treatment containing Streptococcus thermophilus and Enterococcus faecium could reduce LDL-cholesterol by 8% [22]. Similarly positive results were seen in other trials of the same and other probiotic bacteria [23, 24, 25].
In the long-term cross-over study, 29 healthy women aged 19-56 years (15 normocholesterolaemic and 14 hypercholesterolaemic) were fed with 300 g yogurt enriched with Lactobacillus acidophilus 145and Bifidobacterium longum 913and 1% oligofructose. After 21 weeks the mean serum concentration of total cholesterol was not influenced, but the serum concentration of HDL-cholesterol was increased and the ratio of LDL/HDL cholesterol was decreased [26].
The effects of prebiotics on lipid metabolism have also been discussed. Experimental data support the hypothesis that oligofructose inhibits hepatic lipogenesis in rats and consequently induces a significant hypotriglyceridemic effect. The potential mechanisms of this effect include the metabolic or genetic effect of short-chain carboxylic acids low glycaemia and insulinaemia [6, 27].
The prebiotics may also lower both total cholesterol and LDL-cholesterol levels. The possible mechanism of this effect may be accounted for by the activity of propionate. Propionate, a product of oligosaccharide fermentation in the colon, may inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis [27].
Osteoporosis and osteopenia
The scientific literature does not provide reliable data about health-oriented effects of probiotics on calcium-phosphorus metabolism in humans. However, their influence on bioavailability, calcium absorption and bone metabolism has been fully reported.
Several studies have shown that prebiotics may contribute to a reduction in the risk of osteoporosis and osteopenia. The oligosaccharides may increase bioavailability of minerals. Although data on the balance of magnesium, iron and zinc are too preliminary to be considered, scientific evidence does exist to support the effects of inulin-type fructans on calcium absorption in both experimental animals and in humans, and this evidence is considered strong. Some recent studies evaluated factors that affect absorption in the colon rather than in the small intestine. The mechanism of increased calcium absorption in the colon may be accounted for, firstly by higher levels of calcium-binding proteins, and secondly by improved activity of short-chain fatty acids; both of them are formed in the colon from the bacterial fermentation of oligosaccharides [21, 28, 29].
In a cross-over study, young male adolescents during 9 days received a dose of orange juice enhanced with 5 g of oligofructose. In the last 2 days calcium absorption was measured. There was a 12% increase in fractional calcium absorption in the oligofructose group as compared to the control group with no prebiotics. These results show a significant potential role for prebiotics in the achievement of peak bone mass [30].
In another study, in post-menopausal women, increased calcium absorption was noted, with constant calcium excretion in urine, which may suggest increased calcium build-up in bones and/or inhibition of bone tissue resorption [31].
Glucose tolerance and diabetes mellitus
The mechanism of the possible effects of prebiotics on glucose tolerance are not well understood. The possible effects of prebiotics on blood glucose may be accounted for in several ways. The oligosaccharides may delay gastric emptying and shorten small intestinal tract transit time. The possible mechanisms of these effects may be accounted for by the activity of short-chain fatty acids and propionate, produced from the oligosaccharides in the colon [6, 27, 32].
Short-chain fatty acids may inhibit gastric emptying by nutrients reaching the ileo-colonic junction. They may also stimulate contractions of the ileum and shorten ileal emptying.
Propionate may inhibit gluconeogenesis by its metabolic conversion to methylmalonyl-CoA and succinyl-CoA, which could inhibit pyruvate carboxylase. Propionate may also reduce plasma levels of free fatty acids. High levels of free fatty acids lower glucose utilization and induce insulin resistance. Propionate may enhance glycolysis through depletion of citrate in hepatocytes. Citrate is an allosteric inhibitor of phosphofructokinase [6, 33, 34, 35].
Taking into account the great health benefits of dietary modification of the intestinal flora, health promotion authorities recommend regular intake of food products containing probiotics and prebiotics. The most popular are fermented dairy products, such as yogurt, kefir, ´acidofilus´ and ´bifidus´ milk, cottage cheese, and blue and ripening cheese of camembert type. The food market offers three groups of fermented dairy beverages:
– 1st generation beverages (traditional) – containing Streptococcus thermophilus and Lactobacillus bulgaricus yogurt bacteria
– 2nd generation beverages – containing traditional strains and gastrointestinal bacteria (probiotics)
– 3rd generation beverages (non-traditional) – containing exclusively probiotic microflora, without yogurt bacteria.
The nutritional value of fermented dairy beverages is higher than that of fresh milk. The fermentation bacteria favourably influence its composition changes. There ensues a process of lactose to glucose and galactose hydrolysis with lactic acid release. Lactose is partially digested into a food product, and then the lactic acid bacteria produce intestinal lactase, which enables such product intake by people with hypolactasis. The product acidification enables increased protein assimilation. The lactic milk bacteria synthesize the B-group vitamins, significantly increasing their content in the final product (up to tenfold). During milk fermentation the casein and milk whey proteins can release significant amounts of functional peptides. Probiotics are also used as natural food preservatives, inhibiting the development of gastrointestinal infection pathogens through bacteriocin production [36, 37].
Gastrointestinal microflora modification through regular probiotic food intake can protect against gastrointestinal diseases, influence human health status and simultaneously diminish the risk of some chronic civilization diseases. The natural bifidobacterial yogurts of the new generation are particularly valuable as a healthy diet supplement because of their high nutritional value and the probiotic presence. Therefore they should be recommended as an everyday part of the diet of adults and children.
Conclusions
Probiotic food improves human health status and can protect against some gastrointestinal diseases. Regular intake of food containing pro- and prebiotics as an everyday part of the diet is safe and can be recommended for healthy humans. Probiotic food has potential health benefits for prevention of chronic illnesses such as cancer, cardiovascular diseases and osteoporosis, but considerable clinical studies on humans are still needed to confirm this.
Piśmiennictwo
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