Microbiome markers and therapies for autism spectrum disorders
Inventors
Krajmalnik-Brown, Rosa • Kang, Dae-Wook • Park, Jin Gyoon • Labaer, Joshua • Ilhan, Zehra
Assignees
Publication Number
US-11542560-B2
Publication Date
2023-01-03
Expiration Date
2033-03-15
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Abstract
The present disclosure provides for characterization of normal flora and identifying biomarkers in the gut of healthy, neurotypical subjects. Aspect of the disclosure provide for the characterization of the gut microbiome in ADS subjects, characterized by reduced richness and significant loss of the ‘Prevotella-like enterotype’ compared to neurotypical subjects. The relative abundance of genera Prevotella, Coprococcus, Prevotellaceae and Veillonellaceae are significantly lower in autistic children than in neurotypical children. Further, Prevotella, is one of the three main classifiers for the human enterotypes, along with Bacteriodes and Ruminococcus. These three core genera are among main contributors in the principle component analysis. ‘Prevotella-like enterotype’ was absent in the autistic group, while neurotypical samples showed an even distribution among the three enterotypes. The present disclosure provides for an understanding the association between gut microbiota, health, and disease states, and provides for potential diagnostic and therapeutic targets.
Core Innovation
The invention relates to the characterization of the gut microbiome in autism spectrum disorder (ASD) subjects, focusing particularly on the reduced diversity and significant loss of the 'Prevotella-like enterotype' compared to neurotypical subjects. It identifies that the relative abundance of Prevotella, Coprococcus, Prevotellaceae, and Veillonellaceae is significantly lower in autistic children, with the absence of Prevotella being especially notable.
The patent provides assays and therapeutic interventions that detect or quantify these specific bacteria in human subjects, through nucleic acid or protein analysis, and compares the results to a predetermined abundance. If a deficiency is observed, a treatment regimen can be selected or administered, including prebiotic, probiotic, or pharmaceutical modification of the gut microbiota to restore microbial balance or alleviate ASD symptoms.
The invention also addresses the need for better understanding of the role of gut microbiota in autistic subjects, an area previously lacking detailed microbial composition profiles specifically associated with ASD. By identifying specific microbial markers and developing targeted therapies based on the presence or absence of these biomarkers, the disclosure presents methods for diagnosis and treatment of ASD and associated gastrointestinal symptoms.
Claims Coverage
The independent claims cover two main inventive features: the therapeutic administration of Prevotella and the use of Prevotella-containing probiotics in ASD subjects with reduced gut bacterial diversity and abundance.
Therapeutic administration of Prevotella for ASD
A method of treating autism spectrum disorder in a human subject is claimed, comprising administering a pharmaceutical composition with cultured bacteria of the genus Prevotella. The treatment is intended for subjects whose gut microflora has reduced bacterial diversity and lower relative abundance of Prevotella copri or Prevotella paludivivens compared to neurotypical individuals.
Probiotic composition comprising Prevotella for ASD treatment
A method of treating autism spectrum disorder in a human subject is claimed, involving administering a probiotic composition containing bacteria of the genus Prevotella. This is specified for subjects whose gut microflora exhibits reduced bacterial diversity and decreased relative abundance of Prevotella copri or Prevotella paludivivens in comparison to neurotypical persons.
In summary, the inventive features focus on the use of Prevotella, either as a pharmaceutical or a probiotic, for treating ASD in patients with documented reduction in specific gut bacteria and diversity.
Stated Advantages
Enables diagnosis and targeting of specific changes in the gut microbiome associated with ASD, providing new diagnostic and therapeutic targets.
Allows for the modification of the gut microbiota to restore a neurotypical or healthy profile, potentially alleviating ASD symptoms including GI disorders.
Uses Prevotella as a biomarker for a healthy gut and as a probiotic to improve gut function and health.
Documented Applications
Diagnosis of ASD or gut-related symptoms in subjects by quantifying the abundance of Prevotella, Coprococcus, Prevotellaceae, or Veillonellaceae in the gut microbiome.
Therapeutic treatment of ASD using pharmaceutical or probiotic compositions comprising Prevotella for subjects with reduced abundance of this genus.
Treatment of gastrointestinal symptoms associated with ASD, such as constipation, diarrhea, flatulence, and abdominal pain, through modifying gut microbiota.
Use of microbial abundance as criteria for selecting or excluding subjects in clinical trials for ASD or gut-related symptoms.
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