10 September, 2023
Babies and young children with more mature communities of bacteria present in their
gut are less likely to develop allergy-related wheezing or asthma, according to research presented at
the European Respiratory Society International Congress in Milan, Italy [1].
These communities of bacteria, known as microbiota, develop in the human body during the early
years of life and are involved in processes that are helpful to the body, such as synthesising vitamins
and boosting the immune system, or occasionally unhelpful, such as the role they play in
inflammatory bowel disease and stomach ulcers. Babies already have some microbiota in their guts
from their mothers when they are born. The diversity of microbiota increases and matures as they
grow older and are exposed to more different types from sources such as other children, animals,
and different foods.
Dr Yuan Gao, a research fellow at Deakin University, Geelong, Australia, who presented the study,
said: “Our studies on the Barwon Infant Study showed that a more mature infant gut microbiota at
one year of age was associated with a lower chance of developing food allergies and asthma in
childhood. This appeared to be driven by the overall composition of the gut microbiota rather than
specific bacteria. We then hypothesised that advanced maturation of the infant gut microbiota in
early life is associated with decreased risk of allergy-related wheeze in later childhood.”
The Barwon Infant Study (BIS), which has been running in Australia since 2010, recruited 1074 babies
between 2010 and 2013, and researchers have been following the babies as they grow. For this
current study, Dr Gao and her colleagues looked at the bacteria present in faecal samples collected
from the BIS babies one month after birth, six months and one year. At the one-year and four-year
postnatal reviews, the BIS investigators asked the parents to report on whether their children had
developed allergy-related wheeze or asthma in the previous 12 months. They also did skin-prick
tests to see if the children had allergic reactions to any of ten foods and any airborne substances
that can trigger an allergic response, such as rye grass or dust.
In a randomly selected sub-group of 323 children, the BIS team used a DNA sequencing technique to
identify and characterise the gut microbiota. They calculated ‘microbiota-by-age z-score’ (MAZs),
which is a mathematical estimate of the maturity of the children’s gut microbiota.
“We found that if babies had more mature gut microbiota when they were one year old, they were
less likely to have an allergy-related wheeze at one and four years old,” said Dr Gao. “If MAZ
increased within a certain range, known as standard deviation, it halved the risk of allergy-related
wheeze at both these ages. In other words, the more mature the gut microbiota, the less likely were
the children to have allergy-related wheeze. We did not find a similar association with MAZ scores at
one or six months.”
The mechanisms by which mature gut microbiota contribute to preventing allergy-related disease is
not completely understood. “Given the complex origins and development of both gut microbiota
and the infant immune system, it is likely that the protective effect of a healthy gut microbiota
occurs as a result of communities of bacteria acting in multiple different ways, rather than via one
particular mechanism,” said Dr Gao.
“We hope that by understanding how the gut microbiota improves the immune system, new ways of
preventing allergy-related disease such as asthma can be developed. For instance, it might be
possible to suggest ways of advancing the maturation of gut microbiota in early life, which would
lead to fewer children developing asthma and other allergy-related diseases in the future. With so
little known about why babies develop allergies and asthma, more research is needed.”
The researchers are planning to recruit 2000 children from Australia and New Zealand to a new
clinical trial, called ARROW, to see whether giving young children a mixture of dead bacteria, taken
orally, can protect them from wheezing illnesses or asthma by boosting a healthy immune response
to viral infections. Viruses are the commonest causes of childhood illnesses and can lead to chest
infections and wheezing.
“ARROW has the potential to dramatically improve the health of children with recurrent wheeze and
asthma,” said Dr Gao.
Strengths of the study include its design, which allowed researchers to analyse the development of
gut microbiota as the children grew older, and also the fact that the BIS children were drawn from
the general population. Limitations include the fact that the DNA methods used to characterise the
gut microbiota cannot provide insights into the function of the bacteria.
Dr Erol Gaillard, Secretary of the European Respiratory Society group on paediatric allergy and
asthma, and associate professor in child health and honorary consultant in paediatric respiratory
medicine at the University of Leicester and Leicester Royal Infirmary, Leicester, UK, was not involved
with the research. He commented: “Allergy-related illnesses such as asthma and eczema are some of
the commonest conditions affecting children, and the incidences are rising in many parts of the
world. We are not sure why this happens, but theories include smaller families where children are
less exposed to several other siblings and the germs they inevitably carry, less diverse food eaten at
an early age, and less exposure to farm animals in some communities.
“Dr Gao and colleagues report that more mature gut microbiota in early infancy may protect against
the development of wheezing illness and allergies. This fits with some of these other theories
because exposure to a variety of bacteria from an early age is very likely if babies and children are
regularly mixing with other children and animals and are exposed to a larger variety of foods. If we
can find ways to boost the maturity of gut microbiota, this could have a significant effect on the
incidence of allergies, and so it will be interesting to see the results of the ARROW study.”
[1] Abstract no: OA1434 “Late breaking abstract – Gut microbiota maturity in infancy and atopic wheeze in childhood”, by Yuan Gao et al; Presented in session “Latest research on paediatric asthma” at 14.15-15.30 CEST on Sunday 10 September 2023.
https://k4.ersnet.org/prod/v2/Front/Program/Session?e=379&session=16582