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Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

Author information

1
Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, 85287, USA.
2
School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287, USA.
3
Soil, Water and Environmental Sciences, University of Arizona, Tucson, AZ, 85721, USA.
4
Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA.
5
Centre for Digestive Diseases, Five Dock, NSW, 2046, Australia.
6
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, 85287, USA.
7
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, 02114, USA.
8
Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
9
BioTechnology Institute, University of Minnesota, St. Paul, MN, 55108, USA.
10
Center for Immunology, University of Minnesota, Minneapolis, MN, 55414, USA.
11
Integrative Developmental Pediatrics, Tucson, AZ, 85701, USA.
12
Department of Soil, Water and Climate, University of Minnesota, St. Paul, MN, 55108, USA.
13
Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
14
Soil, Water and Environmental Sciences, University of Arizona, Tucson, AZ, 85721, USA. mbsulli@gmail.com.
15
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, 85287, USA. mbsulli@gmail.com.
16
Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA. mbsulli@gmail.com.
17
Department of Civil, Environmental and Geodetic Engineering, Ohio State University, Columbus, OH, 43120, USA. mbsulli@gmail.com.
18
Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA. gregcaporaso@gmail.com.
19
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA. gregcaporaso@gmail.com.
20
Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, 85287, USA. Dr.Rosy@asu.edu.
21
School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, 85287, USA. Dr.Rosy@asu.edu.

Abstract

BACKGROUND:

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

RESULTS:

MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).

CONCLUSIONS:

This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.

TRIAL REGISTRATION:

This trial was registered on the ClinicalTrials.gov, with the registration number  NCT02504554.

KEYWORDS:

Autism spectrum disorders (ASD); Clinical trial; Fecal microbiota transplant (FMT); Gut bacteria; Gut bacteriophage; Microbiome; Virome

PMID:
28122648
PMCID:
PMC5264285
DOI:
10.1186/s40168-016-0225-7
[Indexed for MEDLINE]
Free PMC Article

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