The absence of four strains of intestinal bacteria can make the difference between breathing easily and succumbing to childhood asthma, a new study has shown.
Asthma is now the commonest childhood disease in western countries, and the prevalence of the condition, which causes wheeze, chest tightness and difficulty breathing, has increased up to threefold in the last fifty years.
A number of factors have been implicated in the rise, including antibiotic exposure, lack of breast feeding, excessively hygienic living conditions and birth by caesarian section, which just by itself increases the risk of asthma and allergy by 25%.
What unites these factors is exposure to the microbial world early in life, although exactly how an individual's gut flora, or microbiota, might manipulate the immune system to push development down an allergy-prone path wasn't known.
Now, writing in Science Translational Medicine, University of British Columbia researcher Brett Finlay and his colleagues have identified four bacterial groups which, if missing from the microbiome in the first few months of life, are linked to the development of asthma.
The researchers looked at 319 individuals enrolled in the CHILD (Canadian Healthy Infant Longitudinal Development) study, in which a large group of children were followed from pregnancy though to the age of five and assessed for a range of health outcomes and environmental exposures.
Faecal specimens collected from the children at various ages were examined genetically to profile the diversity and numbers of microbes that were colonising their intestines.
The researchers compared the bacterial signatures from children with and without asthma to look for any differences in the spectrum of microbes detected in the two groups.
Four microbial groups - Faecalibacteria, Lachnospira, Veillonella and Rothia, collectively dubbed "flavour" - FLVR - by the group, if absent at 3 months of age, were strongly linked to the development of asthma.
Alone, these data do not prove that lacking these bugs causes asthma to develop. However, the team then colonised groups of mice with the intestinal bacteria from a 3-month old human baby that subsequently went on to become asthmatic.
To half of these mice the researchers also administered the FLVR microbes before challenging the entire group with a substance that provokes the rodent equivalent of asthma.
The mice that got only the asthmatic human gut bugs developed inflammatory changes in their lungs, but animals also colonised with the FLVR bugs were protected.
"This is the best evidence we have so far that these microbes, present during a critical window period during human development, play a critical role in the development of the immune system," says Finlay.
The Canadian team suggest that their findings could be turned into a test to spot individuals who might be at risk of asthma in later life.
Also, under circumstances where antibiotic treatment is necessary, or in infants discovered to be in the risk category, supplements containing the four key microbes could be given to restore the normal microbial balance and, like the mice in the study, stop asthma developing.