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

Abstract

BackgroundAutism 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.ResultsMTT 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).ConclusionsThis 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 registrationThis trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554 Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0225-7) contains supplementary material, which is available to authorized users.

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…Social deficits in mice (less interest in social interaction, poor memory for social partners) [110,113] Reversal of social deficits in murine models of ASD [111,115] Reversal of antibiotic-induced social deficits in mice [113] Reduced risk for ASD [116] , reduced symptom severity in children with ASD (open pilot) [117] Transplant of standardized human gut microbiota to children with ASD improved ASD symptoms in open-label pilot [118] Pain Visceral hypersensitivity in mice [119] Visceral hypersensitivity in healthy mice [94,120,135] Reversal of visceral hypersensitivity in stressed mice [122] Increased risk for IBS in humans [51] Positive effects on pain in IBS patients [127] Reversal of stressinduced visceral hypersensitivity in rats [121] Reversal of antibiotic-induced visceral hypersensitivity in mice [135] Positive effects on IBS symptoms in humans [127] Transplant from IBS donors increases GI symptoms (accelerated gastrointestinal transit, increased intestinal permeability) in mice [125,126] Transplant from healthy donors reduces GI symptoms (constipation, diarrhea, indigestion, abdominal pain) in children with ASD (open-label pilot) [118] www.advancedsciencenews.com www.bioessays-journal.com been several studies reporting no effect of probiotics on these measures, [99] these disparate results may be explained by straindependent effects or a moderating effect of symptom severity because it has been reported that the beneficial effects are greatest for those with the most negative symptoms at baseline. [100] …”

“…[117] In addition, significant improvements in gastrointestinal and behavioral symptoms were observed in an open pilot of faecal microbiota transplants for children with ASD. [118] …”

Exploring the microbiome in health and disease

“…In a recent small study of 18 children with autism, positive changes in gastrointestinal symptoms and neurological symptoms have been noted after microbiota transfer therapy. 327 …”

Microbiome in psychiatry: where will we go?

“…The bridge to neuropsychiatric diseases has already been built, for example, in Parkinson's disease [6] or multiple sclerosis [7], but also in autism spectrum disorders [8].…”

“…In addition, preclinical studies reveal an influence of the microbiome on various constructs regarding temperament and behavior. A recently published phase 1 study found promising evidence for the fact that repeated fecal microbiome transplantations did not only improve the frequent gastrointestinal symptoms, but also behavioral problems of 18 children with autism spectrum disorders [8].…”