High-level antigen exposure during the first few months of life is suspected of predisposing individuals to allergic sensitisation and, therefore, various atopic conditions such as skin reactions and even systemic or respiratory manifestations. Intestinal inflammation seems to be a predisposing factor in increased sensitisation of a subject, which in turn promotes further inflammation when antigen exposure occurs.
Considering that the gut microflora is an important factor in regulating both the intestinal and systemic immune system, probiotics are used to promote endogenous barrier mechanisms, reduce gut permeability and alleviate intestinal inflammation in patients with atopic dermatitis and food. A 1 -month study of 10 breastfed infants who had atopic eczema and cow’s milk allergy found that L. GG reduced certain faecal inflammatory markers.
Clinical note — The hygiene hypothesis
The intestinal tract is the largest immune organ of the body. It produces more antibodies than any other part of the body and contains 80% of all antibody-producing cells. The intestinal mucosa functions as a barrier against infections, but it also provides communication between the different mucosal surfaces of the body.
At birth, the gastrointestinal tract is sterile. Normal gut flora develops gradually over time and is influenced by factors such as composition of the maternal gut microflora, diet, degree of hygiene, use of antibiotics or other medication, the environment and possibly genetic aspects. Studies in germ-free mice have shown that without these bacteria, the systemic immune system will not function normally.
In the absence of microbes, a mammal develops fewer Peyer’s patches (part of the gut-associated lymphoid tissue) and less than 10% of the number of IgA-producing B cells compared with normal. However, on exposure to a normal microflora, previously germ-free animals develop their immune system very much like other animals. This indicates that the intestinal microflora is instrumental in the proper development of the immune system and has led to the emergence of the ‘hygiene theory of immune disorders’.
More specifically, the hygiene hypothesis suggests that improved hygienic conditions and vaccinations, which reduce early-life exposure to microbes, are associated with a heightened risk of allergic disease and other immune disorders. This is because reduced exposure may result in reduced stimulation of the immune system. As a result, lymphocytes that would normally differentiate to become Th1 type, differentiate to Th2-type cells and produce inflammatory cytokines in the allergic response in much greater quantities. As such, very early stimulation of the immune system is important in dampening the Th2 dominance and reducing the development of IgE-mediated food reactions as well as other allergic reactions. In a closely observed cohort of 329 Finnish children it was shown that the earlier an acute respiratory infection occurred, the greater the protective effect was against atopic eczema.
The obvious solution for increasing microbial exposure without increasing the health risk is the use of prebiotics and probiotics. Supplementation with probiotics has been shown to both reduce the risk and treat the symptoms of childhood eczema (see later).
Modulating the intestinal microflora with probiotics and prebiotics (fibre) may be an effective and safe therapy for the natural development of a balanced immune defence in infants and children. In adults and the elderly, prebiotics and probiotics may be used to improve the general functioning of the immune system.
In a 12-week, double-blind, placebo-controlled, three-stage before-and-after intervention trial of 25 healthy elderly individuals, one-half were given milk containing a specific strain of Bifidobacterium lactis HN019, while the other half were given milk alone. Dietary consumption of the probiotic enhanced immune function of two different types of leucocytes; the degree of enhancement was increased by consuming B. lactis in an oligosaccharide-rich substrate.
In another 7-month, double-blind placebo-controlled study of 571 children in daycare centres in Finland, milkfortified with L. GG reduced the number and severity of respiratory infections. The effects of the probiotic were modest but consistent.
A 9-week, three-stage, pre- and post-intervention trial with 52 healthy middle-aged and elderly volunteers found that dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolysed low-fat milk, enhanced systemic cellular immune responses. The phagocytic activity of peripheral blood polymorphonuclear leucocytes and in vitro tumouricidal activity of NK leucocytes increased by 19% and 1 5%, respectively. The relative level of NK-cell tumour killing activity increased by 71% and 147%.
Probiotics: Dosage Range
• As more information is gathered from probiotic research, it is becoming evident that certain strains or combination of strains are suitable for different conditions. Different strains of probiotics are chosen and combined to produce specific products for diarrhea in children, antibiotic-induced diarrhea, travellers’ diarrhea, inflammatory bowel diseases etc.
• Probiotic doses are usually standardised in terms of the amount of living bacteria per unit of volume. A quality product may contain between 1 x 109 and 1 x 10″ colony-forming units/g; however, the dose required to achieve therapeutic effects varies between strains. If a product contains multiple strains then each strain should be present at levels of 109 to be effective. The viable bacteria are mixed in a suitable matrix, which may contain maltodextrin, amylase and prebiotics such as fructo-oligosaccharides and inulin.
• Supplements are best taken with meals to enhance bacterial survival.
• Diarrhoea: generally Saccharomyces boulardiiand sometimes lactobacilli.
• Atopic dermatitis: generally lactobacilli, sometimes together with bifidobacteria.
• Cholesterol-lowering: lactobacilli are used.
• Urinary tract infection: lactobacilli are used.
• Vaginal candidiasis: lactobacilli are used.
* A serving of yoghurt containing less than 108 viable bacteria is unlikely to have any therapeutic activity beyond acting as a nutritional source.
Clinical note — Dosages tailored to increase probiotic survival
Several attempts have been made to ensure the survival of the probiotics through the acid environment of the stomach and exposure to bile acid. Microencapsulating the probiotics is one method that has been used. Enteric-coated tablets containing probiotics that are gastric-acid resistant have also been produced. More studies, however, are needed to examine the efficacy of these administration forms to deliver and release the probiotic at the appropriate target sites in the gastrointestinal tract. Studies are also needed to establish if such measures are actually necessary. With a suitable matrix, a probiotic powder may survive the passage through the digestive tract without either microencapsulation or enteric-coating of tablets.