You give me fever

When the flowers are blooming and the grass is high, Bill Parry starts sneezing. As allergies afflict more and more Britons, could our germ-free lifestyles be responsible - and if so, could 'friendly' bacteria be the answer?
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Indy Lifestyle Online

For everything there is a season. Now is the hay-fever season - as you'll have noticed, whether you suffer directly or not. For those of you who feel as wretched as I do from dawn till dusk, ready to scratch out my eyeballs, with a wad of tissues at the ready, any medical breakthrough in the fight against allergies would be welcome relief. Also, my eczema is inclined to flare up as the weather gets muggier.

For everything there is a season. Now is the hay-fever season - as you'll have noticed, whether you suffer directly or not. For those of you who feel as wretched as I do from dawn till dusk, ready to scratch out my eyeballs, with a wad of tissues at the ready, any medical breakthrough in the fight against allergies would be welcome relief. Also, my eczema is inclined to flare up as the weather gets muggier.

Hence my joy when I read in The Lancet that Finnish researchers, led by Dr Marko Kalliomaki, have shown that giving a probiotic - in this case, Lactobacillus rhamnosus - reduces the risk of eczema by half in at-risk children of up to four years old.

Ah, probiotics - the latest health buzz-word. Your supermarket's dairy aisle is full of them. But what are they? They're "good" micro-organisms that benefit our health. It's a symbiotic relationship: we give them a home and food and, amongst other things, they contribute to healthy digestion and aid our immune system. The commonest strains in yoghurts are lactobacilli and bifidobacteria, also found naturally in the gut.

I began to read related reports, some of which stated optimistically that the use of probiotics might be extended to treat other allergy disorders. So should I alter my diet to maximise my probiotic intake, with live bacteria yoghurts and drinks such as Actimel? Or take vitamin supplements with probiotics, all rolled into one convenient capsule, such as Microbionta?

The number of people suffering from allergic disorders has doubled in the last few decades in developed Western countries. Many reports claim that allergies affect as many as 40 per cent of children in European and North American inner cities.

In 2002, hay-fever sufferers in the UK coughed up £68m to relieve their symptoms, up by £4m on the previous year, says Sarah Noakes of Information Resources. A recent poll by Boots the chemist showed that 25 per cent of people in their thirties get hay fever. Asked about parents, grandparents and children, respondents said that 40 per cent of their children suffered hay fever, while only 15 per cent of parents and 8 per cent of grandparents had had it.

This rise in allergic disorders has coincided with a fall in exposure to harmless micro-organisms, leading researchers to support a theory called the "hygiene hypothesis". It suggests that the rise in allergic disorders (andautoimmune disorders such as multiple sclerosis, inflammatory bowel disease and Type 1 diabetes) is due to a much reduced exposure in early life to harmless micro-organisms. Our immune systems do not mature properly - they are untrained to respond to real threats, as distinct from harmless or even beneficial bugs.

The theory is supported by many case studies, which found that: young children who had several older siblings, or who attend day-care centres in the first six months of life, have a lower incidence of asthma and Type 1 diabetes than those who didn't; more West German children, who grew up in relatively hygienic conditions, suffered from asthma and atopic allergy disorders than East German counterparts; and an inverse relationship is found between the incidence of allergies and the frequency with which children washed their faces in the UK's western counties and in Germany.

Graham Rook, professor of medical microbiology at University College London and the Royal Free Hospital, says: "One of the mechanisms the immunoresponse system has is to produce an immediate, explosive reaction to invading things. That evolved to deal with things like worms or parasites trying to get into the mucosa of the gut. What is happening now is that that particular part of the immune system is starting to do rather frivolous things, like attacking trivial amounts of pollen, or the neighbour's cat, or whatever. It's an immunological reaction that shouldn't be happening."

We have cells called antigen presenting cells (APCs), which encounter foreign material and present it to lymphocytes called T-cells, which decide how much of a toxic threat it is. They can activate different types of T-cells, depending on the type of threat: T-helper 1 (Th1) cells provide immunity against tuberculosis and most viruses and cancers; T-helper 2 (Th2) cells are typically responsible for parasites and produce immediate, explosive reactions (hence the itchy eyes and runny nose of a hay-fever attack, or the life-threatening symptoms when an asthmatic encounters a cat).

But in our ultrahygienic world, we are bypassing a critical stage in the T-cell cascade of possible reactions - that of T-regulatory cells, which "regulate" the numbers of Th1 and Th2 cells. The hypothesis is that in the absence of exposure to "old friends" - harmless environmental micro-organisms - our T-reg cells are not being activated. "It's when you're not 'turning on' this background of regulatory activity that the Th1 or Th2 cells get out of hand," says Professor Rook. Hence the rise in allergic disorders and autoimmune diseases.

These "old friends" are things such as worms, helminths, parasites, probiotics and saprophytic mycobacteria (mud bugs, related to those that cause TB), to which we would have had routine exposure in our recent and evolutionary past. They have a molecular code, or play a "chord", which APCs recognise as friendly, so T-reg cells are activated, keeping Th1 and Th2 cells in check. But in the absence of these "old friends", there is no T-cell regulation, so Th1 or Th2 cell reactions occur in the presence of foreign material, regardless of whether it's a nasty parasite or harmless pollen or cat dander.

Enter Dr Kalliomaki. By exposing pregnant women and at-risk newborns to L rhamnosus, it seems that the babies' immune systems are maturing in more normally. He expects this positive trend to continue beyond the age of four in these children. "Early administration of L rhamnosus affects the immune system beneficially as to allergic diseases later in life," he believes. Trials will (hopefully) confirm this.

Others, such as Professor Rook, are doing similar work with different organisms, looking for ways to "supplement" and thereby physiologically "educate" our immune systems with bugs we used to be regularly exposed to. His current work deals with a mud bug, Mycobacterium vaccae.

It's early days, and these approaches are crude, bombarding the immune system with whole bugs and massive quantities of them. To get the volumes of L rhamnosus used in Dr Kalliomaki's trials, Professor Rook guesses that you would need to culture vats of yoghurt in your kitchen and consume the bacteria neat.

But almost certainly this research will lead to isolating those "chords" or strands of molecules that will allow the body's immune system to develop properly. Dr Kalliomaki predicts that in the future "we will have some kind of 'vaccines' against allergy", probably "partly composed of gut microbes or their parts". How long will that take? "A decade or two."

Professor Rook sees it happening sooner, "possibly in six years' time," he says. It might be in the form of "new vaccines or new yoghurts, it doesn't matter. It might be probiotics or vaccines. They might spray it in the environment or stick it on doorknobs."

But might these developments with probiotics offer hope to allergy sufferers such as myself, whose immune system is decades past that formative phase? "In a small study with adults suffering from hay fever," Dr Kalliomaki says, "L rhamnosus had no beneficial effects on the symptoms." As if that wasn't disappointing enough, he adds: "During early infancy there may be a 'time window' when [our] immature immune system is more susceptible to environmental, beneficial microbes than later."

Professor Rook is more encouraging. "There's still evidence that these kinds of changes in lifestyle are effective in adults," he says. "Several of our clinical studies have been in adults [and] we do get effects. These were very small trials, but some results were statistically significant and very exciting. We now have bigger trials [an asthma one and an eczema one] with ongoing recruitment, so we shall see. But there is hope for adults. We think you need to be constantly educating your regulatory cells."

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