In a study of children with autism spectrum disorder (ASD), fecal microbiota transplant (FMT) led to significant and lasting improvements in both gastrointestinal (GI) symptoms and ASD-related symptoms, researchers report.
"We were hoping for some improvement in GI symptoms but were surprised to see 80% improvement," Ann Gregory, one of the study's lead authors and a microbiology graduate student at the Ohio State University in Columbus, told Medscape Medical News.
"Further, we were hoping for some improvement in autism symptoms and were pleased to see about a 25% improvement in only 10 weeks that remained after treatment stopped," she added.
The study was published online January 23 in the journal Microbiome.
Many children with autism have chronic GI problems, Gregory said, "and abnormal gut bacteria seem to be a major factor. Previous studies looking at the gut microbiome of children with autism have shown lower diversity in autistic children compared to their neurotypical peers."
Mounting evidence suggests that GI and behavioral symptoms in children with ASD may stem in part from gut microbiota dysbiosis. There is further evidence that FMT may effectively rebalance the gut microbiota and alleviate some GI and ASD symptoms, the researchers note.
To investigate, they treated 18 patients aged 7 to 17 years who had ASD and moderate to severe GI problems with a modified FMT protocol termed microbiota transfer therapy (MTT).
The protocol involved 14 days of therapy with oral vancomycin followed by a 12- to 24-hour fast (clear liquids only) with a bowel cleanse using MoviPrep. On day 16, to repopulate gut microbiota, a high initial dose of standardized human gut microbiota (SHGM) was given either orally or rectally for 2 days followed by daily, lower maintenance oral doses of SHGM coupled with a stomach-acid suppressant for 7 to 8 weeks. The stomach-acid suppressant was used to increase survival of SHGM through the stomach. The children were followed for an additional 8 weeks after treatment ended.
MTT led to substantial changes in GI and ASD symptoms, the researchers report. GI symptoms, as assessed by the GI Symptom Rating Scale (GSRS), improved significantly for abdominal pain, indigestion, diarrhea, and constipation.
The average GSRS score dropped 82% from the beginning to the end of the treatment. The improvement was maintained 8 weeks after treatment stopped (77% decrease from baseline; P < .001). Only 2 of 18 children (11%) achieved <50% reduction in the average GSRS, the cutoff for improvement, and were designated as nonresponders.
Daily stool records showed significant decreases in the number of days with abnormal or no stools (P = .002). These improvements were maintained after 8 weeks of no treatment.
ASD-related symptoms also improved with MTT. The Parent Global Impressions-III (PGI-III) assessment, which evaluates 17 ASD-related symptoms, showed significant improvement during treatment and no reversion 8 weeks after treatment ended, the researchers report.
Of note, there was a significant negative correlation between change in GSRS and PGI-III scores, which "suggests that GI symptoms worsen directly with ASD behaviors, and that these can be altered via MTT," they write.
The researchers also found that scores on the Childhood Autism Rating Scale (CARS), which rates core ASD symptoms, dropped by 22% from beginning to end of the treatment and by 24% (relative to baseline) after 8 weeks of no treatment (P < .001).
MTT was also associated with improvement in the Social Responsiveness Scale, which assesses social skill deficits, and the Aberrant Behavior Checklist, which evaluates irritability, hyperactivity, lethargy, stereotypy, and aberrant speech.
On the Vineland Adaptive Behavior Scale II (VABS-II), which evaluates adaptive behaviors such as communication, daily living skills, and socialization, the average developmental age increased by 1.4 years (P < .001) and across all subdomains during MTT, though the final VABS-II age equivalent remained lower than the patients' chronologic age, the researchers report.
There was no significant difference in clinical outcomes between those who received the initial SHGM dose orally and those who received it rectally.
The MTT protocol was generally well tolerated, with only temporary adverse effects (primarily mild to moderate hyperactivity and tantrums/aggression) at the beginning of vancomycin treatment. No major changes in blood chemistry or long-term adverse effects were noted.
The researchers also noted a rebalancing of the gut following MTT.
They found evidence of "successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks)," they write.
"The increase in diversity of the gut microbiome following treatment shows that ability of bacteria to colonize the new host and recruit new beneficial bacteria such as Prevotella after treatment," said Gregory.
The researchers caution that this was a small, open-label trial that is subject to placebo effects, so the results should be "cautiously interpreted and viewed as preliminary."
"We are now planning a larger phase 2 study (randomized, double-blind, placebo-controlled, multisite) as a next step towards FDA [US Food and Drug Administration] approval. FDA treats this as an investigational new drug. More research is needed before this can be used for treatment," Gregory said.
Reached for comment, Brett Finlay, PhD, microbiologist at the University of British Columbia in Vancouver, Canada, who is known for his work on microbial pathogenicity and microbiota, said, "This is obviously a contentious area, but there is increasing evidence that microbiomes may be involved in autism.
"There have been several studies," Dr Finlay added, "showing that microbes are different in autistic kids, but that doesn't prove causation (they may have different eating habits, etc). However, there are also several anecdotal cases about fecal transfers improving autism. So nothing incredibly novel in this study, but it adds more support to the concept of microbial involvement. As they study longer periods, and more studies pile up, we will learn more about this."
The study was supported by the Arizona Board of Regents, the Autism Research Institute, and the Gordon and Betty Moore Foundation. Several authors have pending/approved patents related to the use of FMT and/or probiotics for various conditions, including autism; have received research funding from Crestovo for FMT research; or are part-time consultants for Crestovo. Dr Finlay is coauthor of the book Let Them Eat Dirt: Saving Your Child From an Oversanitized World (Algonquin Books, United States; Greystone, Canada) about the role microbes play in early child development.
Microbiome. Published online January 23, 2017. Full text
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