Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota.
Kang DW, Adams JB, Coleman DM, Pollard EL, Maldonado J, McDonough-Means S, Caporaso JG, Krajmalnik-Brown R
Sci Rep. Apr 2019. doi: 10.1038/s41598-019-42183-0
COMMENT: In this work the authors show the promissing results of microbiome-based interventions for autism treatment. Bifidobacteria and Prevotella appears to be the most important taxa that increase their relative abundance in the microbiome of autism patients treated with Microbial Transfer Therapy during the 2-year follow-up study that was carried out in this work.
Previously, 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 then 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 problems19. 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.
Two years after the MTT was completed, we invited the 18 original subjects in our treatment group to participate in a follow-up study. The purpose of the study was to conduct a 2-year follow-up on children with ASD who participated in the original study and to determine long-term safety and efficacy of the Microbial Transfer Therapy (MTT).
16S rRNA library for MiSeq Illumina platform according to the protocol from Earth Microbiome Project (http://www.earthmicrobiome.org/protocols-and-standards/16s/). The barcoded primer set 515f -806r was used for pair-ended sequencing to target the 16 s rRNA V4 region.
Based on the Childhood Autism Rating Scale (CARS) rated by a professional evaluator, the severity of ASD at the two-year follow-up was 47% lower than baseline, compared to 23% lower at the end of week 10. At the beginning of the open-label trial, 83% of participants rated in the severe ASD diagnosis per the CARS. At the two-year follow-up, only 17% were rated as severe, 39% were in the mild to moderate range, and 44% of participants were below the ASD diagnostic cut-off scores
Notably, compared to baseline, median relative abundances of Bifidobacteria and Prevotella increased 4-fold and 712-fold at week 10, and 5-fold and 84-fold at two years, respectively.
An increase in Prevotella after MTT is noteworthy, since its lower abundance in feces of children with ASD compared with neurotypical children has been confirmed in two different cohorts. A recent study also found reduced levels of Prevotella in the oral microbiome of children with ASD32. Prevotella may be involved in butyrate production, a key nutrient for the intestinal epithelial cells.
In summary, all 18 participants with ASD were re-evaluated two years after MTT treatment stopped, and we observed significant improvements both in GI and behavior symptoms as compared with baseline measurements collected at the beginning of the original open-label trial. GI benefits were mostly maintained from the end of treatment, and autism symptoms were reported to have improved significantly since the end of treatment.
Changes in gut microbiota persisted at two years, including in overall community diversity and relative abundances of Bifidobacteria and Prevotella. These encouraging observations demonstrate that the intensive MTT intervention is a promising therapy for treating children with ASD who have GI problems. We recommend future research including double-blind, placebo-controlled randomized trials with a larger cohort
FMT: Fecal Microbiota Transplant
ASD: Autism Spectrum Disorders