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

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

Research output: Contribution to journalArticle

284 Scopus citations

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.

Original languageEnglish (US)
Article number10
JournalMicrobiome
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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    Kang, D. W., Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., Khoruts, A., Geis, E., Maldonado, J., McDonough-Means, S., Pollard, E. L., Roux, S., Sadowsky, M. J., Lipson, K. S., Sullivan, M. B., Caporaso, J. G., & Krajmalnik-Brown, R. (2017). Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome, 5(1), [10]. https://doi.org/10.1186/s40168-016-0225-7