Research

Healthy gut,
protected brain
Research into the relationship between gut
health and the developing brain is homing in
on gut-created immune cells that protect
the brain from infection. Dr Ben Marlow
looks at its significance for understanding
how certain subtypes of autism may develop
In my last article in the winter Nowhere is this more evident
Issue of Autism Eye, I commented than in the gut and the brain:
on the work of neuropathologist Dr they are connected by hormones,
Matthew Anderson. I was nerves and, importantly, the
fascinated by his findings that in immune system.
some subtypes of autism there In many of the children I see in
appears to be an inflammatory clinic, the ones with significant
pathology – that is, the activation gastrointestinal issues (pain and
of the brain’s immune system – loose, foul-smelling stools) tend to
and that this behaviour is shared be the children with more
with other conditions such as significant core autism symptoms
multiple sclerosis. and comorbidities, such as poor
Are these neuroinflammatory sleep and a restricted diet.
events more common in people
with defects in the gut/brain
immune barrier? A recent paper Immune cells
authored by a researcher from the originating in
Molecular Immunology Unit at the
University of Cambridge supports the gut migrate to the
this theory. It has demonstrated in blood-brain barrier,
mice that immune cells originating
in the gut migrate to the blood- and have a unique
brain barrier, and that they have a role in immune
unique role in immune surveillance
and protecting the brain from surveillance and
infection. Key to this important protecting the brain”
relationship appears to be gut
biodiversity.1
This research by Zachary Gut cells defend the brain
Fitzpatrick seems to indicate that The membranes surrounding the
impairment to mucosal immunity brain (the meninges) contain a
in the gut also leaves the brain surprising number of immune
more vulnerable to infection cells2, including a population that is
and inflammation. part of the ‘humoral’ (antibody-
Autism and its comorbidities mediated) immune system.
have a significant impact on The team at Cambridge
health, behaviour, learning and University has recently found that
quality of life. In every sense it is in mouse models, a particular
‘multi-systemic’ and these systems antibody, Immunoglobulin A (IgA)
overlap and impact on each other. is produced by plasma cells and

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 Research Crelling Harnesses Ltd.
Tel: 01253 852298 Email: [email protected]
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Crelling Harnesses manufacture a

positioned right on the blood-brain full range of special needs harnesses
barrier. The ‘blood-brain barrier’ is
the important junction that prevents
Research turns to therapy suitable for use on all kinds of
equipment including wheelchairs,
infection reaching the brain. Dr Ben Marlow (MBiochem ABPI MBBS MRCPCH PGCME) is a paediatric
buggies, scooters, shower chairs,
The team showed that these consultant (neurodisability) at Colchester General Hospital, Essex, and
bathing equipment, stair lifts and
special IgA-releasing cells actually clinical director of the hospital’s Synapse Centre, which seeks to translate
seats in cars, buses and aircraft etc.
originated in the gut. They moved biomedical research into practical therapies.
all the way from the gastrointestinal Dr Marlow has a special interest in the neurobiology of
The vehicle harnesses are designed
system to the barrier protecting the neurodevelopmental disorders, especially the fields of neuroimmunology
to be worn in conjunction with
brain. They were also scarce in and metabolism. He is keen to help advocate and advance the translation
the existing safety belts to provide
‘germ-free’ mice (mice without gut of science into treatments for children with neurodisabling conditions,
additional postural support and/
bacteria) and, intriguingly, specific particularly within the field of autism. At the beginning of 2020 he was awarded the Gupta
removal of these IgA antibodies left Foundation Young Researcher Award and National Institute for Health Research (NIHR) local
or to offer a certain degree of
the brain vulnerable to infection at research network principal investigator support funding. restraint when used for those
the blood-brain barrier. passengers with behavioural
Gut-derived IgA plasma cells problems or learning difficulties.
have also been found in the brain inflammation. As discussed in mucosal barrier from being
in other disease states, including previous articles, inflammation in compromised. It also displays a
inflammation in multiple sclerosis3. the developing brain can alter unique ability to survey and
developmental trajectories and can maintain the blood-brain barrier via
Problem with antibiotics be associated with a range of IgA that traps microbes, seen in
Having a diverse gut flora is neurodevelopmental disorders. this research in mice.
increasingly shown to be important Interestingly, replenishing the We make simple belts and full supportive
in health. The Cambridge microbiome in the mice with mouse Microbiome diversity harnesses for all kinds of special needs,
University study authors or human donor gut bacteria In previous articles for Autism Eye, including challenging behaviour
demonstrated that using antibiotics restored the IgA-secreting cells to I have discussed with other
to eradicate gut bacteria in mice the brain. clinicians and researchers their
resulted in a significant reduction experiences of children with
of IgA+ plasma cells in the brain. Maintaining the barriers autism, restricted gut biodiversity
Six weeks after giving the IgA also has an importance in the and the increase in mucosal
antibiotics, the plasma cells were gut, preserving the intestinal permeability in the gut.5,6.
virtually absent. barrier. In autism, papers have The Cambridge paper
It means that using antibiotics, shown there to be a reduction of demonstrates that biodiversity of A HEARTWARMING NEW BOOK
via the effect on the microbiome, mucosal IgA in the gut4, leaving it the gut microbiome generates a FOR CHILDREN WITH AUTISM
leaves the mouse brain more more vulnerable to being breached healthy immunological barrier that
vulnerable to infection and by pathogens. not only protects the gut from
One could therefore postulate invading pathogens, but also
from this research in mice, that with protects the brain. I would stress
Improving gut the bi-directionality of these that this is in a mouse model and
immune cells between the gut and more human studies are required to
health in the brain, depletion of IgA in the show if the same is true in people.
children with autism gut would also lead to depletion of Better understanding and
IgA in the brain. This would then improving gut health in children
could have far- lead not only to increased with autism could therefore
reaching impacts on permeability to infections across potentially have far-reaching
the intestine, but also the brain. impacts on other body systems,
other body systems, The intestinal immune system is including brain health and
including brain health” developed to support the development. More research is
microbiome and prevent the needed in this area.

REFERENCES
1
Fitzpatrick, Z; Frazer, G; Ferro, A et al: ‘Gut-educated IgA plasma cells defend the meningeal venous sinuses’, Nature 587, 472–476 (2020). ‘The sensitive descriptions
Scan the QR code for a throughout the book of what it is
https://doi.org/10.1038/s41586-020-2886-4
FREE colouring sheet like to have autism are accurate and
2
Korin, B et al: ‘High-dimensional, single-cell characterization of the brain’s immune compartment,’ Nat. Neurosci. 20, 1300–1309 (2017), perceptive on so many levels’.
https://www.nature.com/articles/nn.4610 ENDORSED BY TONY ATWOOD,
author of Asperger’s Syndrome: A Guide
3
Rojas, O L et al: ‘Recirculating intestinal IgA-producing cells regulate neuroinflammation via IL-10,’ Cell 176, 610–624.e618 (2019), for Parents and Professionals
https://pubmed.ncbi.nlm.nih.gov/30612739/
4
Mingbang Wang et al: ‘Alteration of gut microbiota-associated epitopes in children with autism spectrum disorders,’ Brain, Behavior, and
Immunity, Volume 75, Pages 192-199 (2019), https://pubmed.ncbi.nlm.nih.gov/30394313/
5
Marlow, B: Autism Eye article – Professor James Adams Interview, issue 35, Autumn 2019, https://www.autismeye.com/subscribe/back- Out now - available from all online bookshops.
issues/
6
Marlow, B: Autism Eye article – Dr Balzola interview, issue 36, Winter 2019/20, https://www.autismeye.com/subscribe/back-issues/

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