Probiotic friendly bacteria may play role in stopping asthma

"'Good bacteria' key to stopping asthma," says BBC News.

Before you go out and buy a year's supply of probiotic yoghurt drinks, it's worth noting a few points that burst the hype bubble.

The news is based on research that found that the lack of some types of bacteria in babies' guts affected their later chances of asthma. However, this was only the case for three-month-olds so the effect, if it exists, is likely to be time-limited.

The researchers did an experiment to demonstrate the concept – by feeding poo from these babies with the relevant bacteria added in to mice that had an asthma-like condition. The offspring of these mice were less likely to have the disease, but this is not the same as a real-life (and potentially unpalatable) experiment in humans.

Asthma has been linked to the "hygiene hypothesis", a theory that says asthma happens when the immune system does not develop properly. Some believe this can happen if a growing baby is not exposed to enough varied bacteria, with antibiotics and caesarean births implicated.

While this new study has provided evidence in support of this theory, it is too early to say the case is proven. We don't know for sure that the levels of these bacteria directly affect risk of asthma in the way suggested.

Where did the story come from?

The study was carried out by researchers in Canada, from the University of British Columbia, the Child Research Institute and British Columbia Children’s Hospital, McMaster University, the University of Toronto, Hospital for Sick Children Toronto, University of Alberta and University of Manitoba. It was funded by the Canadian Institutes of Health Research. The study was published in the peer-reviewed journal Science Translational Medicine.

The story was not widely covered in the media. BBC News published an accurate account of the research, although the headline that these bacteria are "key to stopping asthma" probably overstates the results.

What kind of research was this?

This research included two separate studies. The first was a nested case-control study of children, who were taking part in the bigger, ongoing Canadian Healthy Infant Longitudinal Development study, a prospective cohort study. The second study was a laboratory experiment using mice.

Case-control and longitudinal studies can highlight links between two factors – in this case between the type of bacteria in the gut and the chances of having asthma – but cannot prove by itself that one causes the other. The mouse study shows what happens when you do something to mice, and although it does provide support for the hypothesis, we don't know for certain if the results are directly applicable to humans.

What did the research involve?

For the study in children, researchers selected groups of children at different levels of asthma risk, and analysed samples of their poo (stools), which had been taken at three months and one year of age. They looked for differences between the composition of the gut bacteria in the children at different asthma risk levels.

They later carried out tests to see whether they could find differences in how the children's digestion worked, and whether these could be linked to specific bacteria.

Researchers selected 319 children with relevant samples. They chose all those who fitted the criteria at age one of having both allergic reactions (tested by skin-prick tests) and wheezing, wheeze only or allergic reactions only. They also looked at a sample of children with neither allergy or wheeze, to act as a comparison group. Children with allergic reactions and wheeze have a much higher chance than those without these conditions of being diagnosed with asthma by age five.

The researchers used DNA analysis to identify bacteria in the stool samples and looked for differences in the bacteria present between the groups at highest and lowest risk of asthma. After analysing the bacteria in the gut, researchers looked for differences in products of digestion, including certain short-chain fatty acids. They wanted to see whether the differences in bacteria were linked to differences in the way the children's digestion worked.

In a separate experiment, researchers took mice bred to be free from bacteria and introduced either a stool sample from a child at high risk of asthma, or the same sample with additional bacteria. They allowed these mice to breed, and showed that their offspring carried the bacteria their parents had been given in their guts. The researchers then provoked an asthma-like condition in these offspring, and later provoked an immune response in the lungs of these animals and looked at the resulting levels of inflammation.

What were the basic results?

The 22 children who had both allergic reactions and wheeze at age one, had similar overall amounts and range of different types of bacteria in their stool samples, compared with other children. However, the researchers found that their levels of four particular types of bacteria were much lower, compared to children at the lowest asthma risk.

These bacteria were Faecalibacterium, Lachnospira, Rothia and Veillonella. Babies who had both allergic reactions and wheeze at age one were also more likely by the age of three to either have been diagnosed with asthma or meet criteria for being at high risk, including having had recurrent wheezing episodes.

Importantly, the researchers only found differences between the groups' stool samples when the children were three months old. By one year, the differences had gone.

The researchers also found that children at higher asthma risk had some differences in the way their body digested food, shown by the fact that they had lower levels of a type of short-chain fatty acid called acetate in their stool.

In the mouse experiment, the offspring of mice given the stool sample with additional samples of the four missing bacteria had a lower level of inflammation in the lung, compared to those mice that did not get the additional bacteria. The stool sample with no added bacteria did not have this effect.

How did the researchers interpret the results?

The researchers say their research shows that changes in the gut bacteria in the first few months of life may be "an important factor influencing asthma development", and that the four bacteria they identify may have a "protective role" against the disease.

They went on to say that the findings "enhance the potential for using rationally designed microbe-based therapies to prevent the development of asthma and other allergic diseases that begin in childhood". By this they mean scientists may be able to design a "friendly bacteria" cocktail to be given to children at high risk of asthma, which could reduce their chances of getting allergies and asthma.

Conclusion

This complicated and interesting study sheds light on one potential cause of asthma in children, and points towards areas where research might lead to a treatment to prevent it or reduce its severity. However, this exciting prospect depends on much more work to confirm the results of this study and find out whether what seems to work in laboratory mice can also work in people.

The idea that reduced exposure to bacteria in childhood might increase the chances of getting allergies and asthma has been around for some time. This theory suggests that, for a child's immune system to develop well, it needs to be exposed to a wide variety of bacteria and viruses. If this doesn't happen, the immune system might become oversensitive and react to things that it shouldn't, like certain types of food, or pollen in the atmosphere.

This study suggests that particular types of gut bacteria in the first few months of life might be important for the development of a healthy immune system. However, the study has limitations. While 319 babies were studied, only 22 had wheeze and allergic reactions at age one, and only 19 of these were in the group classified as having, or being at highest risk of, asthma at age three. 

We need to see these results replicated in bigger studies to be sure that all or most babies at risk of asthma have low levels of these specific bacteria. Also, this type of study alone cannot prove that the differences in gut bacteria actually cause asthma. There may be other factors that are important but have not been considered in this study.

We should also be wary of animal studies. While there are a lot of biological similarities between different species, there are differences. In this study, the mice had an asthma-like condition, but the authors acknowledge that this is not exactly the same as human asthma. Also, the bacteria in the guts of the mice in this study and humans are likely to be different. The effect of adding certain bacteria to a mouse gut may be very different if tried in a human. We need to see carefully controlled studies in humans to know whether this treatment could work.

However, the study suggests lots of future research pathways that could increase our understanding of how asthma develops and how it might best be treated, or eventually prevented. For now, we still don't fully understand what causes asthma.