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

Juan Maldonado, Rosa Krajmalnik-Brown, J Gregory Caporaso, Matthew B Sullivan, Karen Schwarzberg Lipson, Michael J Sadowsky, Simon Roux, Elena L Pollard, Sharon McDonough-Means, Dae-Wook Kang, Elizabeth Geis, Alexander Khoruts, Alessio Fasano, Lauren Chittick, Thomas Borody, Ann C Gregory, James B Adams

Journal: Microbiome 2017;5(1):10

PMID: 28122648

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Plain Language Summary

Children with autism spectrum disorders (ASD) often suffer gastrointestinal problems, such as constipation or diarrhea, the severity of which often correlate with ASD severity. This open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on GI and ASD symptoms of 18 ASD-diagnosed children. Treatment involved 2 weeks of antibiotic treatment and a bowel cleanse, followed by extended fecal microbiota transplant using a high initial dose and lower maintenance doses for 7-8 weeks. Results showed significant improvements in GI symptoms, which persisted 8 weeks after treatment ended. Bacterial diversity also increased. Behavioural ASD symptoms also improved significantly and lasted 8 weeks after treatment finished. This exploratory study suggests a promising approach to alter the gut microbiome in ASD subjects, improving GI and behavioural symptoms of ASD. Further clinical research is required.

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 10 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.

Address: Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, 85287, USA.; School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287, USA.; Soil, Water and Environmental Sciences, University of Arizona, Tucson, AZ, 85721, USA.; Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA.; Centre for Digestive Diseases, Five Dock, NSW, 2046, Australia.; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, 85287, USA.; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, 02114, USA.; Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.; BioTechnology Institute, University of Minnesota, St. Paul, MN, 55108, USA.; Center for Immunology, University of Minnesota, Minneapolis, MN, 55414, USA.; Integrative Developmental Pediatrics, Tucson, AZ, 85701, USA.; Department of Soil, Water and Climate, University of Minnesota, St. Paul, MN, 55108, USA.; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.; Soil, Water and Environmental Sciences, University of Arizona, Tucson, AZ, 85721, USA. [email protected].; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, 85287, USA. [email protected].; Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA. [email protected].; Department of Civil, Environmental and Geodetic Engineering, Ohio State University, Columbus, OH, 43120, USA. [email protected].; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA. [email protected].; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA. [email protected].; Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, 85287, USA. [email protected].; School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, 85287, USA. [email protected].

DOI: 10.1186/s40168-016-0225-7

Physical Environment

Infectious Agents

Clinical Imbalances

Neurological Gastro-intestinal

Laboratory Testing

Blood Stool

Nutrition Evidence Keywords

Gutbacteria

Bioactive Substances

Fecalbacteria

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MeSH Terms: Abdominal Pain, Adolescent, Anti-Bacterial Agents, Autism Spectrum Disorder, Bacteriophages, Bifidobacterium, Child, Constipation, DNA, Viral, Desulfovibrio, Diarrhea, Fecal Microbiota Transplantation, Female, Gastrointestinal Diseases, Gastrointestinal Microbiome, Gastrointestinal Tract, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Prevotella, Probiotics