I was thinking yesterday about the
link between eczema (atopic dermatitis) and autism following a comment
regarding a therapy I must have mentioned long ago (l-histidine with zinc). The
therapy did work well for this child.
This then brought me back to one of my
pet subjects, which is the minimization of the risk of future autism. I did
write a section in my book on this subject, but it remains a work-in-progress. My
elder son wants to avoid autism in his future children. If there are simple,
safe, inexpensive steps that can be taken, that also provide broader health benefits
then it would be crazy not to take them.
This brings me to the subject of the
so-called atopic march. I have updated it to include its effects on the brain,
increasing the risk of autism and ADHD and also suggest that in fact there may
be slightly different atopic journeys, rather than a singular march with the
same start and end points.
The atopic march
The traditional "atopic
march" describes the progression from atopic dermatitis (eczema) in
infancy to food allergies, asthma and allergic rhinitis later in childhood.
While this framework has been useful for decades, it may be too simplistic.
Perhaps there is not one atopic march,
but several.
Recent years have seen an explosion of
research into the gut microbiome, immune development, mast cells and
neurodevelopment. Numerous studies continue to investigate probiotics as a
treatment for eczema, allergies and even autism. However, there is a recurring
problem: many of these studies are performed in children who may already be too
old to receive the maximum benefit.
The first few months of life appear to
be a critical developmental window. During this period, the gut microbiome,
immune system and brain are all developing simultaneously. Alterations during
this time may have lifelong consequences.
One particularly intriguing study from
Finland was originally designed to investigate eczema prevention. What makes
this study especially interesting is that the intervention began before many
people would even think about treating the microbiome. Mothers received the
probiotic Lactobacillus rhamnosus GG during the final 2–4 weeks of pregnancy.
After birth, the infants received the probiotic for only the first six months
of life.
Remarkably, this relatively brief
intervention, lasting just a few months around the time of birth, was followed
by measurable differences many years later.
In other words, the researchers were
not treating eczema, ADHD or autism. They were attempting to influence the
earliest stages of microbiome development. This timing is important because the
infant microbiome is initially seeded by microbes acquired from the mother
during birth, breastfeeding and close maternal contact. By giving the probiotic
to both mother and infant, the researchers may have been influencing the
microbial ecosystem at the very moment it was being established.
Years later, when the children were followed into adolescence, the researchers found not only a reduction in eczema but also a surprising reduction in diagnoses of ADHD and Asperger syndrome. If the finding proves to be real, it would suggest that a six-month intervention during infancy may have influenced developmental trajectories more than a decade later. The study was small and requires replication, but the findings were striking.
| Group | Children | ADHD or Asperger syndrome by age 13 | Percentage |
|---|---|---|---|
| Probiotic (LGG) | 40 | 0 | 0% |
| Placebo | 35 | 6 | 17% |
One reason the Finnish study has not
been easily replicated is the sheer difficulty of performing such research. To
repeat the study properly, researchers would need to recruit women during
pregnancy, administer the intervention before birth, continue treatment during
infancy, and then follow the children for 10–15 years while carefully tracking
neurodevelopmental outcomes. Such studies are expensive, logistically
challenging and suffer from inevitable participant drop-out over time.
Furthermore, because probiotics are inexpensive and cannot easily be patented,
there is limited commercial incentive to fund a trial that may take more than a
decade to produce results. As a consequence, many probiotic studies focus on
older children and adults where results can be obtained within months rather
than years, even though the greatest biological impact may occur during the
earliest stages of development.
At the same time, other observations
point in a similar direction:
- Early pet exposure reduces the risk of
eczema.
- Children raised on farms have lower rates
of allergic disease.
- Early probiotic use can reduce the risk
of atopic dermatitis.
- Food allergies are increasingly viewed as
part of the atopic march.
- Autism and ADHD are associated with
higher rates of allergic disease in many studies.
The common denominator may be
early-life immune and microbiome development.
The protective effects of pets and
farm exposure are often discussed in the context of the hygiene hypothesis,
although the modern interpretation is really a microbial exposure hypothesis.
Children growing up around animals are exposed to a much greater diversity of
microorganisms. Rather than overwhelming the immune system, these microbial
exposures appear to help educate and calibrate it. Studies of children raised
on traditional farms consistently show lower rates of eczema, asthma and
allergic disease. The immune system evolved in a world rich in microbial
exposures, and it may require those signals to develop normally.
This brings us to an important point.
The infant microbiome does not arise spontaneously. Much of it originates from
the mother. During birth, breastfeeding and close maternal contact, microbes
are transferred from mother to child. These pioneer organisms help establish
the infant gut microbiome and play a critical role in training the developing
immune system. In many ways, the microbiome acts as one of the earliest
teachers of the immune system, helping it learn the difference between harmless
substances and genuine threats.
This process of immune calibration
appears to occur very early in life. Once established, the microbiome becomes
increasingly stable and resistant to change. This may explain why probiotics
often show their greatest effects when administered during pregnancy or
infancy, while studies in older children and adults frequently produce much
smaller results. By the time many interventions are attempted, the window
during which the microbiome is shaping immune development may already be
closing.
Perhaps the most remarkable aspect of
the Finnish study is not the probiotic itself, but the timing. The intervention
was completed by six months of age, yet the outcomes were measured at 13 years
of age. This is precisely what one would expect if the microbiome plays a role
in calibrating the developing immune system during a narrow critical window
early in life.
Mast cells may also deserve greater
attention. They play important roles in eczema, food allergies, asthma and
anaphylaxis, but they are also found in the gut and nervous system. Some
researchers have proposed that abnormal mast-cell activity could contribute to
neurodevelopmental symptoms in susceptible individuals.
Another clue that early immune modulation may alter the trajectory of the atopic march comes from studies of ketotifen, an antihistamine and mast-cell stabilizer. In one notable study of infants with atopic dermatitis, children receiving ketotifen were significantly less likely to develop asthma during the follow-up period. The researchers also reported improvements in the severity of atopic dermatitis. These findings suggest that, at least in some children, modifying mast-cell activity and allergic inflammation early in life may alter the subsequent progression of allergic disease.
If the classical atopic march can be interrupted before eczema progresses to asthma, it raises a broader question. Could other early interventions—such as probiotics, microbial exposure from pets and farm environments, or targeted immune modulation—also alter developmental trajectories extending beyond allergy and into neurodevelopment in susceptible children?
This raises an interesting
possibility. For a subgroup of children, the atopic march may not end with
asthma and hay fever. Instead, immune dysregulation, microbiome alterations and
barrier dysfunction could also influence neurodevelopment, increasing the risk
of ADHD or autism.
The proposed sequence might look
something like this:
Microbiome disturbance / barrier
dysfunction → Eczema → Food allergy → Mast-cell activation → ADHD / Autism
susceptibility
or perhaps
Microbiome disturbance → Food allergy
→ Eczema → Neurodevelopmental effects
In other words, there may be multiple
entry points and multiple destinations.
Importantly, this hypothesis does not
suggest that eczema causes autism, nor that most children with eczema will
develop autism. Rather, it suggests that some children may share an underlying
biological pathway affecting the skin, gut, immune system and brain.
If this hypothesis contains even a
grain of truth, it has profound implications. It would mean that interventions
aimed at modifying the microbiome or immune system may be most effective during
infancy, before symptoms of autism or ADHD are apparent. By the time a child is
diagnosed at age 3, 5 or 10, the critical developmental window may already have
passed.
The irony is that we continue to
perform large numbers of probiotic studies in older children and adults, where
effects are often modest. The greatest opportunity may lie much earlier, during
the period when the microbiome and immune system are still being assembled.
The challenge for researchers is to
identify which children belong to this subgroup before the window of
opportunity closes.
The classical atopic march has evolved
over time. Perhaps the next evolution will be to recognize that, in some
children, the journey extends beyond allergies and into neurodevelopment.
Conclusion
In the Finnish study, the intervention was actually in both the mother and the infant:
- Mothers took Lactobacillus rhamnosus GG
during the final 2–4 weeks of pregnancy.
- After birth, the infants received the
probiotic until 6 months of age.
It would be very easy to implement this.
Dog and farm animal exposure (pregnant mother and later the baby) might be more difficult for some, but easy for others.
NAC during pregnancy is another simple one. It was also show very effective in reducing miscarriages and increasing the “take-home baby rate.”
We also saw Prof Ramaekers using folinic acid during pregnancy where future parents test positive for folate receptor antibodies. This requires the future parents taking the FRAT test.
In older children and adults probiotics can have a benefit, but the dramatic effect only occurs when given prior to the immune system being (mis)calibrated. In the older age-group it appears that you need something more potent – FMT works in some cases.
The Finnish study only refers to level 1 autism (then called Asperger's syndrome).
I imagine if you could repeat this study and also include all the common issues like
- Dyslexia
- Dyscalculia
- Developmental language disorder
- Dyspraxia (developmental coordination disorder)
- Learning disabilities generally
- Level 2 and 3 autism
you would see some shocking results.
You would not have 0% incidence of each disorder in the probiotic group, but I bet you would see a substantial reduction.
