Abstract
Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
Highlights
The human gut and brain interact in complex ways, and abnormal conditions in the gut may predispose individuals to neurodevelopmental disorders[1,2]
The improvement was on average 58% reduction in Gastrointestinal Symptom Rating Scale (GSRS) and 26% reduction in % days of abnormal stools (Daily Stool Record or Daily Stool Records (DSR)) relative to baseline, and this result is similar to what we observed at the end of treatment
The improvement in GI symptoms was observed for all sub-categories of GSRS as well as for all sub-categories of DSR, the degree of improvement on indigestion symptom was reduced after 2 years compared with weeks 10 and 18
Summary
The human gut and brain interact in complex ways, and abnormal conditions in the gut may predispose individuals to neurodevelopmental disorders[1,2]. We performed a pioneering open-label modified-FMT trial with an intensive combination called Microbial Transfer Therapy (MTT) consisting of two-week vancomycin treatment followed by a bowel cleanse and high dose FMT for 1–2 days and 7–8 weeks of daily maintenance doses along with a stomach-acid suppressant, administered to children with ASD and chronic gastrointestinal problems[19] After this 10-week MTT treatment and an eight-week follow-up observation period (18 weeks in total), we observed an 80% reduction in GI symptoms and a slow but steady improvement in core ASD symptoms. We learned that gut microbial diversity, including potentially beneficial microbes, significantly increased after MTT19 Two years after this original clinical trial was completed, we re-evaluated the participants to determine whether observed improvements in behavior and GI symptoms persisted, and to ascertain the long-term impact of MTT on the gut microbiome of the study participants
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