Methods for treating autism spectrum disorder and associated symptoms

Abstract

The present disclosure relates to compositions and methods for treating autism spectrum disorder (ASD) by restoring an ASD patient's gut microbiota. These methods can be used with ASD patient with or without ongoing gastrointestinal symptoms. Provided here is a method for modulating the abundance of one or more gut microorganisms in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising a fecal microbe preparation to achieve at least a 2-fold change of the abundance of said one or more gut microorganisms, wherein said one or more gut microorganisms are selected from the group consisting of Bifidobacterium, Prevotella, Desulfovibrio, Copprococcus, Clostridium , and Bacteroides.

1 . A method for increasing the abundance of one or more gut microorganisms in a subject in need thereof, said method comprising treating said subject by administering a therapeutically effective amount of a pharmaceutical composition comprising a fecal microbe preparation comprising a substantially complete fecal microbiota from a single donor, wherein said subject exhibits at least a 2-fold increase of the abundance of said one or more gut microorganisms after said treatment as compared to before initiating said treatment, wherein said one or more gut microorganisms are selected from the group consisting of  Bifidobacterium, Prevotella  and  Desulfovibrio.    
     
     
         2 . A method for modulating the abundance of one or more gut microorganisms in a subject in need thereof, said method comprising treating said subject by administering a therapeutically effective amount of a pharmaceutical composition comprising a fecal microbe preparation comprising a substantially complete fecal microbiota from a single donor, wherein said subject exhibits at least a 2-fold change of the abundance of said one or more gut microorganisms after said treatment as compared to before initiating said treatment, wherein said one or more gut microorganisms are selected from the group consisting of  Bifidobacterium, Prevotella, Desulfovibrio, Copprococcus, Clostridium, Eggerthella , and  Bacteroides.    
     
     
         3 . The method of  claim 1 , wherein said method further comprises determining in said subject a relative abundance of said one or more gut microorganisms. 
     
     
         4 . The method of  claim 1 , wherein said subject has an autism spectrum disorder (ASD) and said method improves one or more ASD symptoms. 
     
     
         5 . The method of  claim 4 , wherein said one or more ASD symptoms are selected from the group consisting of gastrointestinal (GI) condition, speech, sociability, receptive language, cognition, irritability, mood, anxiety, lethargy, stereotypy, hyperactivity, and play skills. 
     
     
         6 . The method of  claim 1 , wherein said subject exhibits at least a 10% reduction in assessment score after said treatment as compared to before initiating said treatment based on an assessment system selected from the group consisting of Childhood Autism Rating Scale (CARS), Childhood Autism Rating Scale 2—Standard Form (CARS2-ST), Childhood Autism Rating Scale 2—High Functioning (CARS2-HF), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scale II (VABS-II). 
     
     
         7 . The method of  claim 1 , where said at least 2-fold increase is achieved after 2 or more weeks of initiating said treatment. 
     
     
         8 . The method of  claim 1 , where said at least 2-fold increase is maintained for at least 8 weeks after discontinuing said treatment. 
     
     
         9 . The method of  claim 1 , where said subject exhibits no gastrointestinal (GI) symptom prior to initiating said treatment. 
     
     
         10 . The method of  claim 1 , where said subject further exhibits one or more GI symptoms prior to initiating said treatment. 
     
     
         11 . The method of  claim 10 , where said subject exhibits at least a 50% reduction in assessment score based on the Gastrointestinal Symptom Rating Scale (GSRS) assessment system after said treatment as compared to before initiating said treatment. 
     
     
         12 . The method of  claim 1 , where said method further comprises administering an antibiotic to said subject prior to administering said pharmaceutical composition. 
     
     
         13 . The method of  claim 1 , wherein said pharmaceutical composition is administered orally. 
     
     
         14 . The method of  claim 1 , wherein said fecal microbe preparation is lyophilized. 
     
     
         15 . The method of  claim 1 , wherein said fecal microbe preparation comprises a non-selected and substantially complete fecal microbiota from a single donor. 
     
     
         16 . The method of  claim 1 , wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora and comprises no antibiotic resistant populations. 
     
     
         17 . The method of  claim 1 , wherein said pharmaceutical composition is formulated as an acid-resistant capsule. 
     
     
         18 . A method comprising
 a. determining a relative abundance of one or more gut microorganisms in a subject having an ASD or having an ASD sibling, and   b. administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising a fecal microbe preparation comprising a substantially complete fecal microbiota from a single donor to achieve at least a 2-fold change of the abundance of said one or more gut microorganisms, wherein said one or more gut microorganisms are from a genus selected from the group consisting of  Clostridium, Bacteroides, Bifidobacterium, Prevotella, Eggerthella , and  Desulfovibrio.      
     
     
         19 . The method of  claim 18 , wherein said subject having an ASD exhibits no gastrointestinal symptom. 
     
     
         20 . The method of  claim 18 , wherein said subject having an ASD does not exhibit one or more, two or more, three or more, four or more gastrointestinal symptoms selected from the group consisting of abdominal pain, reflux, indigestion, irritable bowel syndrome, chronic persistent diarrhoea, diarrhoea, flatulence, constipation, and alternating constipation/diarrhoea.