Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review

**Background:** Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with a global prevalence of 0.37%. The gut-brain axis is implicated in ASD pathogenesis, and fecal microbiota transplantation (FMT) may improve symptoms by restoring gut microbial balance. This systematic review evaluated the effect of FMT on core and associated symptoms of ASD in children.

**Methods:** A systematic literature search was conducted in Embase, PubMed, Web of Science, and Cochrane Library from inception to October 6, 2022. Two reviewers independently screened records and extracted data. Inclusion criteria: children <18 years with ASD, FMT as intervention, and ASD rating scale outcomes. Five studies met criteria: two prospective open-label studies (Kang et al. 2017, USA, n=18; Li et al. 2021, China, n=40), two retrospective observational studies (Zhang et al. 2022, China, n=49; Pan et al. 2022, China, n=42), and one case report (Huang et al. 2022, China, n=1). No randomized controlled trials were identified. Meta-analysis was performed on three studies (Kang, Li, Zhang) using fixed-effects models. Primary outcomes were changes in Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Social Responsiveness Scale (SRS) scores.

**Key Results:** All five studies reported significant post-FMT improvement in ASD symptoms. In the prospective open-label studies: Kang et al. reported CARS score decreased from baseline 39.67±5.30 to post-treatment 34.06±4.56 (p<0.001) and to 8-week follow-up 33.69±5.38 (p<0.001); SRS decreased from 116.17±24.16 to 97.78±27.13 (p<0.001); ABC decreased from 63.58±29.95 to 47.75±32.33 (p<0.01) and to 47.86±27.92 at follow-up (p<0.01). Li et al. reported ABC decreased from 86.08±21.45 to 67.25±19.01 (p<0.001); CARS decreased from 37.55±7.16 to 28.25±6.15 (p<0.0001). In retrospective studies: Zhang et al. reported CARS in the constipation group decreased from 35.25±4.36 to 32.5±3.1 after second course (p=0.015); ABC decreased from 56.21±16.08 to 46.54±16.54 (p=0.046). Pan et al. found ABC and CARS scores decreased with increasing FMT courses, with significant differences between adjacent courses for ABC (second vs. first: -6.50 vs. -5.00, p=0.045; third vs. second: -14.04±16.62 vs. -8.83±13.96, p=0.022). Gastrointestinal symptoms improved by ~80% (Kang) and 35% (Li). Sleep disturbance scores (SDSC) also improved. No severe adverse effects were reported; mild effects included hyperactivity and aggression.

**Clinical Implications:** FMT shows potential as a safe and effective intervention for improving core ASD symptoms, gastrointestinal issues, and sleep disturbances in children. However, the evidence is limited to observational studies and a case report, with no randomized controlled trials. The authors emphasize that rigorously designed, double-blind, placebo-controlled trials are necessary to confirm efficacy and safety before FMT can be recommended as a standard treatment for ASD.