Combined Oral Fecal Capsules Plus Fecal Enema as Treatment of Late-Onset Autism Spectrum Disorder in Children: Report of a Small Case Series

Abstract

Background. Studies have shown that children with autism have greater numbers of the order Clostridiales, Sutterella spp., Ruminococcus torques and Desulfovibrio. Probiotic therapy reduces autistic-like symptoms in mice and vancomycin treatment temporarily ameliorates autism behaviors in a case series. Here we report on the use of combination oral and enema fecal microbiome transplant (FMT) for treating late-onset autism spectrum disorder (ASD) in children. Methods. Nine subjects, all with ASD were aged 2, 3, 5, 5, 6, 8, 8, 11 and 21 years of age at time of treatment. Patient fecal samples were collected prior to treatment, post oral vancomycin treatment (7-10 days) and post FMT. Patients ingested >6 mL of ultracentrifuge concentrated fecal organisms from healthy donor stool in 12-24 over encapsulated gelatin capsules, followed 4h later by an enema of 300-500 mL of fecal slurry. The next day FMT with capsules was repeated. Analysis of the gut microbiome was carried out in a subset of patients. This was done using a combination of culture techniques and 16S rRNA sequence analysis of individual isolates and of the community at large by polymerase chain reaction amplification and sequencing of V3-V4 region of the 16s rRNA gene on the Illumina MiSeq platform. Behavior was monitored informally, before and after treatment, primarily by the childrens' parents. Results. FMT was well-tolerated in all subjects and no adverse effects were reported. ASD symptoms were not changed in the 21 year old (y.o) subject, markedly improved in 1 of two 8 y.o. subjects, both of whom required re-administration of fecal capsules, and markedly improved in younger subjects on a more long-lasting basis. Comparing pre-and post-FMT fecal samples by 16S sequence analysis indicated that Bacteroides, Barnesiella, Parabacteroides, Sutterella, Parasutterella, Clostridales and Erysipetotrichales were most altered. Culture results on 1 subject indicated 108 CFU/g of stool of Clostridium bolteae associated with concurrent ASD symptoms, which was absent post FMT. Identification of bacteria associated with concurrent ASD symptoms in other patients is ongoing. Conclusion. Introduction of a new healthy bowel flora from healthy donors by FMT appeared to benefit autistic symptoms in younger children. Randomized, double-blind controlled trials are of interest.