Correlation Between Gut Microbiota And Autism Spectrum Disorders And A Pilot Study About Fecal Microbiota Transplantation For Children With Autism Spectrum Disorders

Bacground:Children with autism spectrum disorders(ASD)often suffer gastrointestinal problems.Several previous studies have reported abnormal fecal microbiome in children with ASD,but no studies in China have been reported.Recently,a small open-label clinical trial with combined treatments called as microbiota transfer therapy(MTT),improved the symptoms of ASD and evaluated gut microbiota alterations.Objective:To analyze the gut microbiota differences between children with autism spectrum disorders and healthy children and to establish a diagnostic model of microbiome for predicting ASD.To explore the efficacy of solely fecal microbiota transplantation(FMT)for children with ASD and to evaluate impact of FMT on gut microbiota.Methods:Analysis of gut microbiota differences between children with autism spectrum disorders and healthy children.From October 2016 to January 2017,17 patients with autism spectrum disorder(3-7 years old)were enrolled.The 17 healthy children matched with the age,gender,nationality,and region were enrolled in the control group.The stool samples were obtained at three time points within ten days,namely the first day,the fifth day,and the tenth day.And as of September 2017,24 more autism spectrum disorder patients(3-7 years old)and 20 healthy controls were enrolled.The stool samples were obtained at a random time.A total of 41 patients with autism spectrum disorders and 37 healthy controls were enrolled.16S ribosomal RNA(16S rRNA)gene sequencing was carried out.In our study of fecal microbiota transplantation for children with autism spectrum disorders,4 young children(4-6 years old)with autism spectrum disorders received single fecal microbiota transplantation via both gastroscopy and colonoscopy and 2 month follow-up.Autism symptoms were evaluated by autism behavior checklist(ABC)and Childhood Autism Rating Scale(CARS).16S ribosomal RNA(16S rRNA)gene sequencing and metagenome analysis analyzed fecal microbiota changes before and after FMT.Results:Analysis of gut microbiota differences between children with autism spectrum disorders and healthy children.The results of 16S rRNA gene sequencing showed differences of Dorea,Lachnospira,Veillonellaceae,Polymorphum,and Bulleidia.A diagnostic random forest prediction model for intestinal microbiota was established.The area under the curve was 80%.Clinical assessments showed that behavioral ASD symptoms improved significantly by autism behavior checklist(ABC)2 months after treatment.Both 16S rRNA gene sequencing and metagenome analysis indicated that FMT remodeled the gut microbiota of 4 children with ASD.The relative abundances of Acidaminococcus,Bifidobacterium,Catenibacterium,Lactococcus and Megasphaera five genera were shifted after FMT.Patients with better improvement of autism symptoms had more abundant Bacteroidetes with a decrease of Firmicutes/Bacteroidets ratio.Conclusions and Relevance:The gut microbiota is closely related to autism spectrum disorders,and the intestinal flora may become a new biological marker for the diagnosis of autism spectrum disorders.FMT is an emerging medical treatment which can improve autism symptoms and remodel the gut microbiota in children with autism spectrum disorders(ASD).