Treating childhood allergy with gut microbes: facts or fiction?
Authors: B. Björkstén
Journal: British Journal of Dermatology (2011)

What do allergies, diabetes, inflammatory bowel disease and obesity have in common? They are all associated with inadequate regulation of immune responses to normally innocuous antigens, and the prevalence seems to increase similarly in affluent societies.1 Animal studies confirm that microbes are essential for the development of a normal immune regulation2 and, according to one hypothesis, modern living is associated with too little microbial stimulation early in life when immune regulatory functions mature.3 The perspective that the gut microbiota may have important roles, both for human health and disease, is by no means a new concept, as around a century ago Elie Metchnikoff suggested that eating certain live micro organisms might promote health.4 Despite this, for many years there was little interest in this concept among researchers and it is only over the last 15 years that it has become accepted that the gut microbiota is an integral component of the host defence system. As a consequence, the use of probiotics and prebiotics in medicine has become a ‘novel old approach’. The total mucosal surface area of the adult human gastrointestinal tract is up to 300 m2, making it the largest body area interacting with the environment. It is colonized with over 1014 micro organisms, corresponding to more than 10 times the total number of cells in the body.5 There have been several studies published over the past 10 years showing that the composition of the gut microbiota differs between healthy and allergic infants and in countries with a high and low prevalence of allergies.6, 7 Differences are apparent within the first week of life,8 that is, they may precede clinical symptoms. It has even been shown that during pregnancy, the vaginal flora of mothers of children who develop asthma by the age of 5 years differs from that of mothers whose children do not develop asthma.9 These findings may offer an explanation for the association between birth through caesarean section and an increased risk of allergic disease.10, 11 All these observations prompted an interest to explore the potential of treating allergy by the administration of probiotic bacteria in infancy. Several clinical studies using different strains of bacteria suggested a modest prevention of infantile eczema, while effects on established eczema are more controversial (summarized in Tang et al.12 and Lee et al.13). While some differences between the outcomes of the various studies may be attributed partly to the use of different strains, there are other differences that may be more significant. Thus, in most studies showing a reduction in the incidence of eczema, the probiotic bacteria were also given to the mothers during the last month of pregnancy, while in the negative studies treatment was only given postnatally to the babies.14 So far, much of the research efforts have focused on isolating and characterizing individual strains with probiotic properties. This is the traditional reductionist approach in biomedical research. From an evolutionary point of view, however, microbial ecology and diversity, rather than any single strain, would be a more logical starting point in the search for preventive and therapeutic strategies based on the gut microbiota. This notion would be supported by the fact that, despite numerous studies from several countries confirming differences in the composition of the gut microbiota between allergic and nonallergic individuals, there is no particular strain or species that consistently differs between the two groups. The only consistent difference between healthy and allergic children is that bacterial diversity is more pronounced in the former. This was observed even in studies where there were no differences in the prevalence or number of any particular microbe.15 Several meta-analyses confirm that several stains of Lactobacillus or Bifidobacterium have clinical effects in various clinical conditions, such as shortening the duration of infectious diarrhoea in infants and young children,16 prevention of necrotizing enterocolitis17 and reduction of diarrhoea associated with antibiotic treatment in children18 and adults.19 Interestingly, these analyses suggest that none of the tested strains is clearly superior to other strains. Thus, differences in study outcomes are of a similar magnitude for studies testing the same strain as for studies employing different strains of probiotics. This would suggest that the effects are not predominantly strain specific but are secondary to a yet unknown ecological impact of the administration. The likelihood that microbial ecology and diversity might be more important than any single bacterial strain would argue in favour of a more general approach to modify the microbiota. Prebiotics are indigestible carbohydrates that when eaten provide the gut microbiota with nutrition, thus conceivably facilitating a health-promoting flora. Unfortunately, most studies of prebiotics so far had a limited scope and were often underpowered. There is thus only limited support for the efficacy of prebiotic compounds in the prevention or treatment of infantile eczema.20, 21 A third, theoretically attractive approach to modify gut microbiota would be to combine prebiotic compounds with one or several probiotic strains. Although most studies employing this symbiotic approach had only modest quality, there are some encouraging results reported.22 The article in this issue of the BJD23 is of considerable interest as it is the first controlled study comparing a symbiotic and a prebiotic mixture. Unfortunately the study does not answer whether prebiotics only had an effect, as there was no untreated group for comparison, nor a group of children receiving only the strain of L. salivarius included in the symbiotic preparation. Much remains to be studied before the precise role of the gut microbiota in health and disease can be defined. It is reasonable to suggest that further studies of the microbial ecosystem, employing new powerful analytical tools, will reveal knowledge that may profoundly affect treatment and prevention of several diseases associated with a modern life style. From what we know today, early infancy is a critical period for modulation of the gut microflora. It is therefore reasonable to suggest that any efficacy of pre-, pro- and symbiotic preparations in the prevention or treatment of eczema and other allergic diseases would mostly be limited to infancy, i.e. at a time when they exert an influence on the development of immune regulation. B.B. has been a speaker at meetings sponsored by several companies selling probiotic and prebiotic products.