A new study shows that the amount of Bifidobacterium in the gut during a child’s very first week of life is linked to the risk of attention-deficit/hyperactivity disorder (ADHD) at the age of 10 years. The finding suggests that signalling molecules from gut bacteria may influence brain development during a particularly sensitive window immediately after birth, says a researcher.
What happens in the gut during a child’s very first week of life may shape development many years later.
A new study in Denmark suggests that higher levels of the substance indole-3-lactic acid (ILA) in the blood of newborns are linked to an increased risk of an ADHD diagnosis at the age of 10 years.
ILA is a signalling molecule produced when certain types of Bifidobacterium metabolise the amino acid tryptophan in the gut. Bifidobacterium, in particular, has traditionally been regarded as one of the most beneficial types of bacteria in infants’ guts.
The finding therefore suggests that it is not only a question of which bacteria a child acquires but also when they appear.
“It is surprising that Bifidobacterium, which is normally considered to be among the most beneficial types of bacteria in an infant gut, appears to be a risk factor when found in high levels very early in life. We have followed these children very closely throughout childhood and now tried to take a step back to see whether early-life factors influence the risk of later ADHD. One thing that appears to play a role is the composition of the gut microbiota during the very first week of life,” says a researcher behind the study, Professor Jakob Stokholm from COPSAC at the University of Copenhagen, Denmark.
The research has been published in Molecular Psychiatry, in a collaboration between COPSAC, CINS (Clinical Intervention and Neuropsychiatric Schizophrenia Research) and Department of Biology, University of Copenhagen.
The signal only appeared in the first week of life
The researchers monitored the children’s gut bacteria throughout their first year of life using stool samples collected at one week, one month and one year. They then compared the bacterial composition with the risk of having a diagnosis of ADHD at age 10 years.
The study included just under 700 children from the COPSAC2010 cohort. Of these, 593 underwent thorough psychiatric assessment at the age of 10 years. Sixty-five children – corresponding to just under 11% – received a research diagnosis of ADHD, all validated by a child psychiatrist.
The association with Bifidobacterium only appeared in samples from the child’s first week of life. By one month and one year, the researchers could no longer detect the signal.
According to Jakob Stokholm, the finding may suggest that the brain passes through a particularly sensitive developmental window in the very first days after birth, during which signals from the gut may more easily influence development.
“Normally, we say that high levels of Bifidobacterium are a good thing for infants, but like so many other things, this is probably about balance and timing. There is something about this very early colonisation that we need to understand better. It may well be that children who have high levels of Bifidobacterium in their gut very early in life have an overall different timing of their gut colonisation, which perhaps could affect brain development in a way we do not yet understand,” he says.
Heel-prick blood samples pointed to a possible biological mechanism
The researchers then turned to the children’s heel-prick blood samples to investigate whether the bacteria might leave chemical traces in the blood that could potentially affect the brain. This blood sample is taken from all newborns in Denmark a few days after birth and stored in Denmark’s National Biobank.
They found that levels of ILA were linked both to the amount of Bifidobacterium in the gut and to the risk of developing ADHD later in life.
For every 10-fold increase in ILA levels, the risk of an ADHD diagnosis was 4.23 times higher.
This suggests that ILA may be one of the signalling molecules linking gut bacteria to brain development.
“Bifidobacterium produces ILA, and this metabolite appears to explain part of the link with ADHD. ILA can affect receptors that are also found in the brain, providing a biologically plausible pathway from gut bacteria to brain development,” explains Jakob Stokholm.
The same signal appeared in two independent cohorts
The researchers then investigated whether they could detect the same signal in other groups of children and adults.
One group was the older COPSAC2000 cohort, whose participants are now adults. Here, the researchers found an association between ILA levels in heel-prick blood samples and ADHD symptoms in adulthood.
In the Danish iPSYCH twin cohort, which included 464 participants, the association was also significant. The risk of ADHD was 2.54 times higher for every 10-fold increase in ILA levels.
According to Jakob Stokholm, it is unusual for a microbiome finding to remain so consistent across children, adults and twin studies.
“When we find the same association in three groups, including adults and twins, it suggests that ILA and ADHD are linked in a way that goes beyond a single cohort. This makes us more confident that the signal is real and not just a random finding,” he says.
Researchers now want to identify the specific bacteria behind the signal
Bifidobacterium is among the types of bacteria that particularly thrive in a child’s gut during breastfeeding. However, according to Jakob Stokholm, the findings should not be interpreted as an argument against breastfeeding.
The study merely shows an association and cannot therefore determine whether the bacteria directly contribute to the development of ADHD.
The next step is therefore to map the bacteria’s DNA in greater detail to identify the specific types of Bifidobacterium driving the signal.
“We should definitely not start advocating for people not to breastfeed. What we have found is an interesting association that we now need to investigate further. We will carry out deeper bacterial sequencing so that we can hopefully identify the specific types of Bifidobacterium associated with the risk along with their functions. This is about understanding how the first bacteria to colonise the gut may influence brain development. In the long term, this may bring us closer to understanding how neurodivergence such as ADHD arises,” concludes Jakob Stokholm.
