Changes in gut microflora caused by widespread use of antibiotics and today's high-fat, low-fibre diet could be responsible for a major increase in allergies in recent years, say researchers.
A US team is the first to link gut health to an allergic response in the lung.
Their results, published in the current issue of Infection & Immunity (73, pp30-38), show that changes in the gut microflora of mice following antibiotic use caused an overzealous allergic response.
The findings have implications for foods and supplements that can help balance gut health, already worth some £111 million in the UK alone during 2002, and forecast by Datamonitor to reach £159.3 million by 2007.
"Our research indicates that microflora lining the walls of the gastrointestinal tract are a major underlying factor responsible for the immune system's ability to ignore inhaled allergens," said Gary Huffnagle, an associate professor of internal medicine and of microbiology and immunology at the University of Michigan.
"Change the microflora in the gut and you upset the immune system's balance between tolerance and sensitization."
To test their hypothesis, Huffnagle and colleagues gave normal Balb/C laboratory mice a five-day course of antibiotics, which killed their gut bacteria, followed by a single oral introduction of the yeast Candida albicans. Increased growth of C. albicans in the gut is a common side-effect of antibiotics.
After stopping the antibiotics, they inserted ovalbumin - a commonly used experimental allergen derived from egg whites - via the nasal cavities of all the mice in the study.
The antibiotic-treated mice showed increased airway hypersensitivity to ovalbumin compared to mice that had not received antibiotics.
The results confirmed previous experiments, in which the researchers used a genetically different strain of laboratory mice [C57BL/6] and a different type of allergen - mold spores - instead of ovalbumin.
This research, published in the August issue of the same journal, was the first study linking changes in GI tract microflora to an allergic response in the lung.
"In our new study, we found that differences in host genetics and the type of allergen used didn't matter. The immune responses were literally identical," Huffnagle said.
"It confirms our earlier findings that gut microflora are the key to maintaining a balanced immune response, that changing the composition of microflora in the gut predisposes animals to allergic airway disease, and that allergic sensitization can occur outside the lungs."
Over the last few decades, asthma and allergies have increased significantly throughout Europe, with an average 10 per cent of children now suffering from asthmatic symptoms. But in western Europe, the symptom rate is up to ten times that in eastern countries.
For 1995-1996, the International Study of Asthma and Allergies in Childhood (ISAAC) found prevalence of self-reported asthma symptoms in children aged 13-14 years at 2.6-4.4 per cent in Albania, Romania, Georgia, Greece and the Russian Federation. But these rates reached 32 per cent in Ireland and the United Kingdom. This suggests that a western lifestyle is associated with allergic diseases in childhood.
"If lungs are repeatedly exposed to an allergen, regulatory T cells learn to recognize the allergen as not dangerous and something that can be safely ignored," Huffnagle said.
"Most researchers think that tolerance develops in the lungs, but we believe it actually occurs in the gut. When immune cells in the GI tract come in contact with swallowed allergens, that interaction triggers the development of regulatory T cells, which then migrate to the lungs."
The researchers believe that dietary changes like taking antibiotics, switching from breast milk to formula, or eating a high-sugar, low-fat diet can impact tolerance.
"One short course of antibiotics is not going to give everyone allergies," Huffnagle explained. "But if you are taking antibiotics while your diet consists of white bread and fried food, you are not going to maintain the healthy microflora balance you need to maintain tolerance. If you inhale mold spores or pollen during this period, our studies indicate you are much more likely to become sensitized to them."
The researchers are planning to investigate whether changing only the diet of the experimental mice will alter gut microflora and change the immune response to allergens in the same way as antibiotics.
They will also look at how probiotic supplements can affect this microbial balance.