FMT Effects and microbiota changes following oral lyophilized fecal microbiota transplantation in children with autism spectrum disorder (May 2024, n=38, 1x/4 week for 12 weeks)

Fecal Microbiota Transplants

Michael Harrop

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https://www.frontiersin.org/articles/10.3389/fped.2024.1369823/full

Very mild benefits. Standard poor donor criteria.

Background and purpose: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders that is characterized by core features in social communication impairment and restricted, repetitive sensory-motor behaviors. This study aimed to further investigate the utilization of fecal microbiota transplantation (FMT) in children with ASD, both with and without gastrointestinal (GI) symptoms, evaluate the effect of FMT and analyze the alterations in bacterial and fungal composition within the gut microbiota.


Methods: A total of 38 children diagnosed with ASD participated in the study and underwent oral lyophilized FMT treatment. The dosage of the FMT treatment was determined based on a ratio of 1 g of donor stool per 1 kg of recipient body weight, with a frequency of once every 4 weeks for a total of 12 weeks. In addition, 30 healthy controls (HC) were included in the analysis. The clinical efficacy of FMT was evaluated, while the composition of fecal bacteria and fungi was determined using 16S rRNA and ITS gene sequencing methods.


Results: Median age of the 38 children with ASD was 7 years. Among these children, 84.2% (32 of 38) were boys and 81.6% (31 of 38) exhibited GI symptoms, with indigestion, constipation and diarrhea being the most common symptoms. Sample collections and assessments were conducted at baseline (week 0), post-treatment (week 12) and follow-up (week 20). At the end of the follow-up phase after FMT treatment, the autism behavior checklist (ABC) scores decreased by 23% from baseline, and there was a 10% reduction in scores on the childhood autism rating scale (CARS), a 6% reduction in scores on the social responsiveness scale (SRS) and a 10% reduction in scores on the sleep disturbance scale for children (SDSC). In addition, short-term adverse events observed included vomiting and fever in 2 participants, which were self-limiting and resolved within 24 h, and no long-term adverse events were observed. Although there was no significant difference in alpha and beta diversity in children with ASD before and after FMT therapy, the FMT treatment resulted in alterations in the relative abundances of various bacterial and fungal genera in the samples of ASD patients. Comparisons between children with ASD and healthy controls (HC) revealed statistically significant differences in microbial abundance before and after FMT. Blautia, Sellimonas, Saccharomycopsis and Cystobasidium were more abundant in children with ASD than in HC, while Dorea were less abundant. After FMT treatment, levels of Blautia, Sellimonas, Saccharomycopsis and Cystobasidium decreased, while levels of Dorea increased. Moreover, the increased abundances of Fusicatenibacter, Erysipelotrichaceae_UCG-003, Saccharomyces, Rhodotorula, Cutaneotrichosporon and Zygosaccharomyces were negatively correlated with the scores of ASD core symptoms.


Conclusions: Oral lyophilized FMT could improve GI and ASD related symptoms, as well as sleep disturbances, and alter the gut bacterial and fungal microbiota composition in children with ASD.


Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, www.chictr.org.cn.

Selection of stool donor and FMT preparation​


The medical histories of the volunteers who underwent stool donor screening were reviewed and the laboratory test results were gathered.

To be included as stool donors, individuals had to meet the following criteria: age between 15 and 30 years; overall good health; body mass index (BMI) ranging from 18.5 kg/m2 to 23.9 kg/m2; and regular bowel movements occurring once or twice per day with a Bristol stool score of type 4.

Exclusion criteria included a previous history of GI or chronic systemic disease, malignant neoplasm or had received radiochemotherapy; combined with any ongoing diseases; the use of antibiotics, probiotics, prebiotics, proton pump inhibitors, immunosuppressant agents or blood products during the past 3 months; positive serum results for hepatitis A, B, or C, human immunodeficiency virus, syphilis, Epstein-Barr virus and cytomegalovirus; positive results of feces testing for bacteria, viruses and parasites, and detection of multidrug-resistant genes such as extended-spectrum beta-lactamases, carbapenemases and resistance to colistin (21).

We recruited two donors in our study after screening.
 
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