Amoxicillin and Autism

After contracting strep throat, John Rodakis’s son was put on a 10-day course of amoxicillin, currently one of the most popular antibiotics prescribed for children in the United States. No one would have expected what happened next.

The child, who had been diagnosed with moderate-to-severe autism earlier that year, began displaying changes in his behavior on day 4 of treatment.

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“The first thing we noticed was that he had lots of energy—almost hyper—which was unusual for him, as he was usually a very low-energy kid,” Mr. Rodakis explained by e-mail. “He began making eye contact, which he had all but stopped making about a year prior. He seemed calmer and less fussy. His speech improved rapidly. Previously, he rarely initiated speech and tended to answer questions with one-word answers. As time passed on the antibiotic, he began initiating more speech and stringing together words into complete sentences. Each passing day that he was on the amoxicillin, we saw additional gains.”

Although the child stopped making new gains after completing the course of antibiotics, he retained most of what he had gained, he noted.

“His improvement sparked in me an interest shedding light on the possible links between autism and the microbiome,” said Mr. Rodakis, Founder and CEO of N of One: Autism Research Foundation, who has a career in venture capital and private equity, much of it focused on medical technology.

While reviewing the medical literature, Rodakis came across only one directly relevant study in which the antibiotic vancomycin was administered to a small group of children with severe autism, resulting in a marked improvement in autism symptoms in 80% of the patients.

“When I discovered [the vancomycin study] and heard that many other parents and clinicians had had similar experiences, I was confused,” he said. “Why wasn't there additional research into this phenomenon?”

This inspired Mr. Rodakis to embark on a quest to better understand what had happened to his son while taking amoxicillin “in the hopes that we could learn something that would shed more light on how autism works,” he explained.

His journey was chronicled in a special issue of Microbial Ecology in Health and Disease titled “The Microbiome in Autism Spectrum Disorder”.

“Repeated studies have shown that the gut microbiota in children with autism is different than that of their typically developing peers, but we don't understand how these differences arise or what they mean,” he pointed out. “The gut microbiome is critically important in health and development in ways that we are just beginning to understand. MUCH more research is needed.”

According to Mr. Rodakis, the next step is to conduct more research to understand why this phenomenon occurs in some children and how prevalent it is, since these are both unknown.

“I would love to see a clinical research trial that evaluates autism antibiotic responders before and after antibiotics on multiple fronts: blood chemistry, metabolomics, proteomics, gut bacteria changes to see what is changing,” he added. “Somewhere in that analysis could be a clue on what is ultimately driving ASD [autism spectrum disorder] symptoms and could lead to a real breakthrough in our understanding.”

Mr. Rodakis and Dr. Richard Frye, Arkansas Children’s Hospital Research Institute and University of Arkansas for Medical Sciences, assembled an interdisciplinary group of experts approximately one year ago to discuss ways to further investigate the antibiotic effect documented in the vancomycin study.

They then decided to organize a conference on autism and the microbiome in collaboration with several leading autism researchers, Mr. Rodakis explained. The objectives of the conference were to increase awareness of these possible links and to present a forum in which members of the scientific community could meet together to exchange ideas on the subject. Parents were encouraged to attend the conference.

“Dr. Richard Frye suggested that this group submit articles for a special issue [of Microbial Ecology in Health and Disease] devoted to the subject,” he said. “I was honored and humbled that they would ask me to contribute an article as well.”

His intent while writing his article was “to highlight this phenomenon so the next time a parent observes this or a clinician hears a story like ours, they understand that this is not an isolated incident and hopefully that can lead to better research.”

Mr. Rodakis has the following take-home messages that he wishes to offer clinicians:

• “Be open minded, not dismissive of parents’ claims of things that may help or make their child’s autism symptoms worse. Autism is almost certainly a heterogeneous disorder and the mainstream model of genes driving brain wiring which drives behaviors may not be correct for all cases of autism. We need to be open to other paradigms and demand research that looks at autism from multiple fronts.”
• “We should be very, very careful about repeated rounds of antibiotics in very young children. Beyond the obvious concerns about promoting resistance, to use a baseball analogy, we are in the first inning in terms of understanding the important roles the gut microbiome plays in health, disease, and overall development. Parents need to understand that each round of antibiotics brings with it risks.
• “Be aware of the limitations of the double-blind, placebo-controlled trial in the autism population. While it is our gold standard of efficacy, its usefulness requires a homogenous population, which autism is almost certainly not. For example, the finding that a certain diet does not benefit the entire population of autism patients does not mean that for some subset of patients it will not produce great improvements. We simply do not know enough to be able to subtype autism yet.”
• “As I state in my article, I am not advocating the use of antibiotics as a treatment for autism, but they may be a useful research tool in a controlled clinical research setting.”

-Meredith Edwards White

References:

1. Rodakis J. An n=1 case report of a child with autism improving on antibiotics and a father’s quest to understand what it may mean. Microb Ecol Health Dis. 2015 Mar 24. [Epub ahead of print]

2. Sandler RH, Finegold SM, Bolte ER, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15(7):429-435.