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This case report describes a novel therapy for patients with severe autism spectrum disorder (ASD) that is worth further investigation. A 19-year-old male adolescent with ASD, who was not responding to standard treatment received fecal microbiota transplant (FMT) using donor material from his typically developing female sibling. The patient's ASD symptoms were assessed by assessors who were blind to the patient's past ASD symptomatology. Assessors used the Childhood Autism Rating Scale (CARS), an observation-based rating scale to assess developmental delay in children with autism (range of CARS scores is 15 - 60; a score > 28 is indicative of autism; higher score is positively correlated with degree of severity), at baseline and again at six timepoints post-FMT. The patient experienced marked improvements in microbiome diversity and composition over the year and a half period that followed the FMT procedure. Additionally, the patient who was previously nonverbal said his first two words and experienced a reduction in aggression 1-month post-FMT. To the authors' knowledge, this is the first report to demonstrate the use of familial FMT in an adolescent patient with ASD. Given that ASD symptom improvements post-FMT tend to occur in younger patients, the authors hypothesize that the use of a familial donor may be an important factor that contributed to the improved outcomes experienced by this older child., Competing Interests: Sabine Hazan is CEO of Ventura Clinical Trials and ProgenaBiome and owner of Microbiome Research Foundation. Sabine Hazan declares that she has a pecuniary interest in Topelia LLC USA. She has patents relevant to microbiome testing and fecal matter transplant. Drs. Haroon and Jordan performed psychological and neurological evaluation on the case and have no conflict of interest to disclose. Dr Walker has no conflict of interest., (Copyright 2024, Hazan et al.)

Background: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions., Methods: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured., Results: Patients (Pts.) 1 and 2, but not Pt. 3's stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment., Conclusions: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study., Competing Interests: Drs. S. Hazan, B. Barrows, A.J. Papoutsis and T. Borody have corporate affiliation to ProgenaBiome™. Dr. S. Hazan has additional corporate affiliation to Ventura Clinical Trials and Topelia Therapeutics Inc. Dr. T. Borody has additional corporate affiliation to Topelia Therapeutics Inc. Dr. S. Dave has corporate affiliation to North End Advisory, LLC and McKesson Specialty Health. No products of these affiliated companies were used in this study., (Copyright 2021, Hazan et al.)