Investigation Of Short-Term Effect Of Washed Microbiota Transplantation On Children With Autism And Differences In Efficacy Of Single Donor And Multi-Donor

Background:Autism spectrum disorder is a serious neurodevelopmental disorder,which no very effective treatment.Relatively effective treatments for autism include non-pharmacological interventions(behavioral therapy,speech and social therapy),as well as drug and diet,but no drugs have been approved to treat the core symptoms of autism.Due to the limited efficacy,high incidence of adverse events and lack of benefits to the core symptoms of ASD,drug therapy has not been widely used.The comprehensive evidence for the efficacy of non-drug therapy for ASD is also limited.At present,a small number of clinical studies have confirmed the efficacy of fecal microbacteria transplantation in autistic patients,but there is little clinical evidence,and there are no studies to explore the impact of donor-related factors on the efficacy of ASD.Washing microbacteria transplantation is an automatic preparation method based on automatic purification system to enrich microbiota from faeces,which can significantly reduce FMT-related adverse events.The purpose of this study was to further explore the short-term efficacy of WMT in the treatment of autistic patients,WMT-related adverse reactions and the difference between single donor and multi-donor.Objective:The main purpose of this study is to explore the short-term clinical effect and adverse reactions of washing bacteria transplantation in autistic patients and whether there is any difference between single donor and multi-donor.Methods:(1)Retrospective consecutive incorporated in March 2020,March2022,the first hospital affiliated to guangdong pharmaceutical university continuity for WMT 2 treatment treatment.(2)Basic information(including sex and age of patients),autism score(ABC,CARS),sleep score(SDSC)before WMT treatment,4weeks after the end of the first course and 4 weeks after the second course of treatment,and adverse reactions related to WMT treatment were collected.10 g feces were collected before treatment and 4 weeks after the end of the second course of treatment for 16 s RNA sequencing to understand the changes of flora structure before and after WMT treatment.Results:(1)General information: A total of 44 patients(38 males and 6females)who met the diagnostic criteria of WMT were included in this study,with an average age of(6.25 ±3.36).They all completed two courses of WMT treatment,of which 22 patients were in the single-donor treatment group and 22 patients in the multi-donor treatment group.There was no statistical difference in age,gender,CARS score,ABC score and SDSC score between the two groups before treatment.(2)Overall clinical efficacy: after two courses of WMT treatment,44 patients with ASD severity CARS score,ABC score and children sleep disorder scale score showed a continuous downward trend compared with the baseline.Four weeks after the end of the first course: The total ABC score decreased from(61.41 ± 22.00)to(53.73 ± 20.43)(P <0.05),in which sensory,exercise and self-care improved more significantly.The CARS total score before treatment and the end of the first treatment course were compared with 35.5(34.00,38.50)vs34.00(31.63,36.00)(P<0.001),where interpersonal relationship,imitation,physical application ability,relationship to non-living objects,adaptation to environmental changes,and overall impression improvement were more obvious.The total SDSC score decreased from 51.61 ± 14.22 to 48.27 ± 14.18(P<0.05).Four weeks after the end of the second treatment,the single-donor and multi-donor scores decreased in ABC score(-10.36± 18.36vs-9.90 ±11.28),CARS score(-2.52±2.63vs-1.89 ± 2.92),SDSC score(-5.36± 11.10vs-5.64 ± 11.29),with P-value greater than 0.05.(3)Comparison between single-donor group and multi-donor group:there was no significant difference in the improvement of clinical symptoms and sleep between the two groups after two courses of WMT treatment.Four weeks after the first course of treatm ent,compared with the baseline before treatm ent,the single donor group and the m ulti-donor group scores were all decreas:the scores of A B C score(-8.27± 18.37vs-9.09± 11.01)and CARS score(-2.07± 2.64vs-2.16± 3.01),SDSC Total score(-3.00± 6.48vs-3.68± 12.69).No significant comparison between single donor and multi-donor groups,Pvalue is greater than0.05.Four weeks after the second course of treatm ent,com pared with the baseline before treatm ent,the single donor group and the m ulti-donor group scores were all decreas:the scores of A B C score(-10.36 ± 18.36vs-9.90 ± 11.28),CARS score(2.52± 2.63vs-1.89± 2.92),SDSC score(5.36 ± 1 1.10vs5.64 ± 11.29).No significant comparison between single donor and multi-donor groups,P-value is greater than0.05.(4)Adverse reactions related to WMT treatment : there w ere few adverse reactions and no serious adverse reactions related to WMT treatment.After WMT treatment,diarrhea occurred in 5 cases(0.9%),fever in 4 cases(0.7%),periumbilical abdominal distension and abdominal pain in 1 case(0.1%).All the above symptoms im proved within 48 hours after symptom atictreatment,and the total incidence of adverse reactions was2.09%.(5)Flora sequencing: after WMT treatment,the alpha diversity of fecal flora in the effective group increased significantly(species richness index ob served＿otus),while the species richness index decreased in the ineffective group,suggesting that the increase of fecal flora alpha diversity after WMT treatment may be related to the curative effect.In the clinical effective group of WMT,the abundance of Subdoligranulum 、 Eubacterium＿＿coprostanoligenes＿group 、Collinsella 、 Ruminococcus＿torques＿group 、 Coprococcus 、Paraprevotella 、 gordonibacter 、 Senegalimassilia 、 UCG＿003 、G CA＿900066575 、 UCG＿010 increased significantly,while the abundance of active Ruminococcus＿＿gnavus＿group 、Pseudomonas 、 erysipelatoclostridium 、 Odoribacter decreased significantly after treatm ent,suggesting that the change of the abundance of these flora after WMT treatment may be related to the curative effect.Conclusion:(1)After two courses of WMT treatment,the ABC score,CARS score and SDSC score all decreased compared with that before treatment,indicating that the core symptoms and sleep disorders of autism patients can be improved quickly after WMT treatment,with good short-term efficacy.(2)Compared with single donor and multiple donor groups,there was no significant difference in ABC score,CARS score and SDSC score improvement after two courses of WMT treatment,indicating that multiple donors or single donors may have little impact on efficacy.(3)WMT treatment for children with autism is safe,with few adverse reactions.(4)After WMT treatment,the increase of alpha diversity of fecal flora and the change of some microflora abundance may be related to the curative effect.