to treating it has also been persistent. This has prompted a large number of
researchers to explore the condition using novel approaches.
Behavioral therapy, speech and social therapy,
psychiatric medications, and dietary and nutritional approaches are the
treatments currently used in treating ASD. Nonetheless, there are no approved
medical treatments available for treating the core symptoms of ASD which
include difficulty in social communication and repetitive behaviors.
Microbiota Transfer Therapy (MTT) MTT, a special type of fecal
initially pioneered by
Dr. Thomas Borody, an Australian gastroenterologist has been highly beneficial
in treating children diagnosed with ASD in the long term. Autism symptoms and
gut health have improved and the improvements have also persisted in the long
term after the treatment, which is significant.
research angle involving the gut microbiome appears very promising in treating
. Gut microbiome is the collection of microbes in the intestines
that helps in digestion, training the immune system and preventing excessive
growth of harmful bacteria. The gut
microbiomes also affect brain communication and neurological health, recent
There is growing interest worldwide about the notion that
changes in normal gut microbiota could be accounted for triggering a wide range
The research team from Arizona State University, Rosa
Krajmalnik-Brown, James Adams, Dae-Wook Kang - also the lead author, have
demonstrated the benefits of the Microbiota Transfer Therapy (MTT) in a new
study. The study, "Long-term benefit of Microbiota Transfer Therapy in Autism Symptoms
and Gut Microbiota," has been published in the Scientific Reports.
Learnings from the Study
of the initial improvements in gut symptoms continued to remain even after two
years post-treatment. A steady reduction of ASD symptoms
during the treatment and over the next two years were reported by the parents
as well. A 45 percent reduction in the core symptoms of ASD was noted by a
professional evaluator at two years post-treatment
as compared to when the treatment began.
"We are finding a very strong
connection between the microbes that live in our intestines and signals that
travel to the brain,"
said Krajmalnik-Brown, Professor,
Biodesign Swette Center for Environmental Biotechnology at the Biodesign
Institute and ASU's School for Sustainable Engineering and the Built
Environment. "Two years later, the
children are doing even better, which is amazing,"
the association between autism and gastrointestinal (GI) problems,
Krajmalnik-Brown said, "Many kids with
autism have gastrointestinal problems, and some studies, including ours, have
found that those children also have worse autism-related symptoms. In many
cases, when you are able to treat those gastrointestinal problems, their
Around 30-50 percent of people with
autism have chronic gastrointestinal (GI) problems,
mostly constipation and diarrhea
or either, that can last for several
years. This will result in continuous discomfort and pain which in turn could
lead to irritability, decreased attention and learning, and negatively impact
behavior as well.
earlier study had found temporary improvements in GI and autism symptoms when
just an antibiotic, Vancomycin
used. The benefits were only short term despite continued use of
research team was faced with the question of what's going on in the gut, how
does it affect both physical and behavioral symptoms of autism, and how a
long-lasting treatment could be developed. The work of Krajmalnik-Brown, Kang and Adams has exhibited that it is possible to 'donate' a more diverse
set of bacteria into the patient and improve gut health by transferring healthy
microbiota to individuals missing specific gut bacteria.
Thomas Borody's Contribution to the
Microbiota Transplantation (FMT)
was initially developed by
Professor Thomas Borody in Australia. He has overseen close to 18,000 FMTs for
various illnesses at the Centre for Digestive Diseases in Sydney since 1987. In
Australia, he established the use of FMT for colitis and
Clostridium difficile infection, and was also the first to use oral FMT to
treat children with ASD.
a single dose of FMT was typically sufficient to treat C. Difficile infections,
this was not enough for Borody's patients with autism who were far harder to
treat. They required FMT every day for three months and eventually, there were significant improvements in both GI and autism symptoms.
used this experience to lead the design of the clinical treatment used for this
study at ASU. Pre-treatment with Vancomycin, a bowel cleanse, a
stomach acid suppressant, and fecal microbiota transfer daily for seven to eight
weeks were all part of the 10-week MTT approach.
"This exploratory, extended-duration
treatment protocol thus appears to be a promising approach to alter the gut
microbiome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms,
ASD symptoms, and the microbiome all persisted for at least eight weeks after
treatment ended, suggesting a long-term impact,"
concluded an initial
open-label study led by Krajmalnik-Brown and Adams, published in the journal Microbiome
in 2017. Whereas the present study shows that the benefits persisted at
least two years post-treatment.
microbiome of children with autism was compared to those in typically
developing children by the ASU team and differences were noted. Low diversity
in gut microbes and depletion of certain strains of helpful bacteria, such as Bifidobacteria
were found in children with autism at the start of the
"Kids with autism are lacking
important beneficial bacteria, and have fewer options in the bacterial menu of
important functions that bacteria provide to the gut than typically developing
diversity as well as the presence of Bifidobacteria
the helpful bacteria
in the gut, significantly increased following the FMT treatment; diversity was
higher and the beneficial microbes continued to be present even after two
"We originally hypothesized that our
therapy would be efficient to transform the dysbiotic gut microbiome toward a
healthy one. In our original paper in 2017, we reported an increase in gut
diversity together with beneficial bacteria after MTT, and after two years, we
observed diversity was even higher and the presence of beneficial microbes
said Kang. While this may be one of the reasons
behind the success of the improved gut health, additional mechanistic studies
would be required to define specific roles of gut microbes in the context of
autism, he added.
Effectiveness of the Treatment
work done at ASU goes beyond merely treating patients, also focusing on
developing better formulations and optimize dosing based on knowledge gained
from the treatment.
"Understanding which microbes and
chemicals produced by the microbes are driving these behavioral changes is at
the heart of our work,"
Krajmalnik-Brown said. T
he study demonstrated that two years after treatment stopped the
participants still had an average of a 58 percent reduction in GI symptoms
compared to baseline. Additionally, the parents of most participants reported
'a slow but steady improvement in core ASD symptoms,' the team's new
about the dedication of the families to the research, Adams said, "Every family completed the study, and every
family returned two years later for a follow-up evaluation." "The treatment was
generally well-tolerated with minimal adverse effects,"
on the study's achievement, Borody said, "This
is a world-first discovery that when we treated the gut bacteria in these
children during our clinical trial two years ago to reset their microbiome with
FMT, positive results are still continuing to be improving two years from the
original treatments. I would call it the highest improvement in a cohort that
anyone has achieved for autism symptoms."
Significant Findings from the Study
compared to the baseline, there was a 45 percent decrease in ASD symptoms,
professional evaluations revealed. Though there may be some placebo effect,
most of the effect appeared to be real, the team observed. While 83 percent of
the participants were rated as having 'severe' autism when the study began,
only 17 percent were 'severe,' 39 percent 'mild/moderate' and 44 percent below
the cut-off for mild ASD, at the end of it.
Caporaso, a co-author on these studies, and a leading expert in microbiome data
science from Northern Arizona University helped in analyzing the microbiome
data to better understand bacterial changes as a result of MTT.
Krajmalnik-Brown, Kang and I are excited about the results, but we want to
caution the public that we need larger clinical trials for this to become an
Adams. Safe and effective treatment requires professional expertise. The
GI distress is improved by the MTT technique
by introducing key strains of
beneficial bacteria and helping in raising the levels of biodiversity within
the gut, boosting health overall in turn.
The Research Team
James Adams, whose daughter was diagnosed with autism, had both professional
and personal reasons to pursue ways to help children with autism because of his
first-hand knowledge of the situation. He is a President's Professor at the
School for Engineering of Matter, Transport and Energy and also the programme
chair of Materials Sciences at ASU. Adams is also the President of the Autism
Society of Greater Phoenix, one of the biggest parent support groups in
"Dr. James Adams is the reason why I
started working on autism,"
"I had the methods to do all of the measurements
and assessments in the microbiome part of the work, and he had the autism
recruitment, supervising clinical work and ASD assessments and guiding the
patients through the trials were handled by Adams and the microbiome
evaluations and plan of the study were done by Krajmalnik-Brown.
the study participants exhibited chronic GI symptoms including chronic constipation
and/or chronic diarrhea
from infancy. Certain parents noted that their children's behavior had improved
over time, extending the benefits of the treatment beyond just physical
"It is very unusual to see steady
gradual improvement after the conclusion of any treatment. We only conducted
the long-term follow-up study after several families told us that their child
was continuing to improve significantly,"
study data suggests that MTT treatment technique made the gut environment
thereby improving both the GI and ASD symptoms long term,
Birth via C-section, reduced breastfeeding, higher
intake of antibiotics, and decreased fiber intake by mothers and their children
were some of the common traits shared by the trial
participants, all of which lead to limited biodiversity in
their gut bacteria, Adams mentioned. The small
sample size and the open-label nature of the study, call for more
research in order to validate if the MTT technique could be therapeutic.
optimal dose and treatment duration followed were 'first generation' estimates
in the initial study and were sufficient to substantially benefit 90 percent of
the children. The team is currently working on optimizing the dosing and
treatment duration in order to improve the benefits further and to ascertain if
booster doses may be required in some cases.
- Autism symptoms reduced nearly 50% two years after fecal transplant - (https://biodesign.asu.edu/news/autism-symptoms-reduced-nearly-50-two-years-after-fecal-transplant)