Autism Symptoms Alleviated with Fecal Microbiota Transplantation

Study finds fecal transplants benefit both gastrointestinal and neuro-psycho-social symptoms

By Mark Davis, ND

Reference

Kang DW, Adams JB, Gregory AC, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10.

Design

Prospective, open-label, uncontrolled pilot study

Participants

Eighteen children between the ages of 7 and 16 with an autism spectrum disorder (ASD) diagnosis and moderate to severe gastrointestinal (GI) problems. Twenty age- and gender-matched neurotypical children without GI disorders were monitored during this time as a comparison group.

Primary Outcome Measures

  1. The primary outcome was change in GI symptoms as measured by parents using a revised version of the Gastrointestinal Symptom Rating Scale (GSRS). Response was defined as a minimum 50% reduction in the average GSRS.
  2. The secondary outcome was change in neuro-psycho-social symptoms as measured by a professional evaluator using the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS), and by parents using the Parent Global Impressions-III (PGI-III), the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale II (VABS-II).
  3. The authors also looked at the bacterial gut microbiomes of the ASD and neurotypical children at baseline and 10 additional times throughout the experiment, and at the viral microbiome at 2 points.

Study Medication and Dosage

The intervention consisted of:

  • Vancomycin 40 mg/kg by mouth each day in 3 divided doses (</= 2g/d) x 14 days
  • Omeprazole 20 mg by mouth each day for 62 days (starting on day 12 of vancomycin, ending on day 74, last day of FMT)
  • Macrogol polyethylene glycol (variable dose as per body weight) on day 15 only (one day after last dose of vancomycin)
  • Oral fecal microbiota transplantation (FMT). FMT material was produced by filtering screened human stool to 250 microns under N2 gas, then centrifuging at 6,000xg to create a pellet consisting of >99% bacteria. Participants were quasi-randomized into 1 of 2 groups:
  • Group 1: Oral/oral delivery: 2.5 trillion fecal-derived cells suspended in chocolate milk, milk substitute, or juice given by mouth in 3 divided doses on day 16 and again on day 17, then 2.5 billion fecal-derived cells suspended in chocolate milk, milk substitute, or juice given by mouth once per day on days 18-74.
  • Group 2: Rectal/oral delivery: 2.5 trillion fecal-derived cells suspended in glycerol & normal saline given rectally on day 16, then 2.5 billion fecal-derived cells suspended in chocolate milk, milk substitute, or juice given by mouth once per day on days 18-74.

Key Findings

Population analysis

The ASD group included more individuals who were delivered by C-section, used non-standard formula during infancy, and had food allergies and eczema, but there were no differences between the ASD group and the neurotypical group in age, gender distribution, body mass index, or antibiotic usage in the first 4 years of life. Children with ASD had significantly shorter duration of breastfeeding and marginally lower fiber consumption than neurotypical children. Mothers of children with ASD consumed an average of 6.2 grams of fiber per day (± 1.3 g), while mothers of neurotypical children averaged 8.6 grams per day (± 1.3 g). This was a statistically significant difference (P<0.01)

Delivery method

There were no significant differences in clinical outcomes between the initial oral FMT and the initial rectal FMT.

Safety and tolerability

All subjects in the ASD group completed the 18-week treatment and observation period. The only adverse effect noted was a temporary increase in hyperactivity and aggression at the beginning of vancomycin treatment.

Change in gastrointestinal symptoms

There was significant (P<0.001) improvement in abdominal pain, indigestion, diarrhea, and constipation as per the parentally evaluated GSRS. Those improvements remained significant even 8 weeks after treatment stopped. Sixteen of the 18 (89%) children with ASD achieved a greater than 50% reduction in average GSRS, which was the cutoff for response.

Change in neuro-psycho-social symptoms

There was a significant (P<0.001) 22% decrease in the professionally evaluated CARS score from baseline to end of treatment, with no regression in the 8 weeks after treatment.

GI and neuro-psycho-social symptoms slowly improved over the 10-week FMT period and persisted through 8 weeks of follow-up.

There were significant changes in parentally evaluated PGI-III (P<0.001), SRS (P<0.001), ABC (P<0.01), and VABS-II (P<0.001) scores. VABS-II, which evaluates communication, daily living, and socialization skills, found that the average developmental age increased by 1.4 years across all subdomain areas.

Stool analysis

At baseline, the ASD group had significantly less diverse fecal microbiome than the neurotypical group, but at the end of the study the 2 groups were statistically indistinguishable: 15/16 responders and 1/2 nonresponders in the ASD group had fecal microbiomes as diverse as those in the neurotypical group.

Fecal samples from the ASD group at the end of treatment and 8 weeks after the end of treatment revealed at least partial engraftment of the donor bacterial community. Changes in ASD-group fecal microbiome included a fourfold increase in Bifidobacterium and significant increases in Prevotella and Desulfovibrio. Bifidobacterium and Prevotella have long been considered possible mutualists in the ASD population, but Desulfovibrio is generally considered to be commensal or pathogenic; the significance of this increase is unknown.

Practice Implications

In an earlier open-label trial of 8 of vancomycin for ASD children, neuro-psycho-social symptoms improved, as per CARS and other scales. However, the improvement was lost by 2 weeks after the end of treatment.1 In contrast, in the trial reviewed here, GI and neuro-psycho-social symptoms slowly improved over the 10-week FMT period and persisted through 8 weeks of follow-up. This persistent benefit compared with a similar trial makes it less likely that the benefits observed in this open-label trial were placebo or regression to the mean.

Legislative guidelines regarding FMT restrict North American clinicians to only providing FMT to patients with a Clostridium difficile infection that is not responding to standard therapies. An oral FMT solution like the one used here is expensive, time consuming, and requires some scientific and technical savvy to produce at home, which has been an insurmountable obstacle to all of my patients except a few who were also physicians and were willing and able to properly filter, centrifuge, and preserve screened donor stool for the benefit of a family member.

Home FMT retention enemas, on the other hand, are much more affordable, less time consuming, and involve little more scientific or technical know-how than many food recipes. Home FMT enemas are being done at home about 10,000 times each year in the United States alone.2

Improper FMT screening or preparation techniques could potentially cause harm, but communicating safe home FMT technique and facilitating FMT donor screening can result in safe home FMT.3 I’ve helped facilitate hundreds of home FMT retention enemas in my practice, and the types and frequency of adverse events I’ve observed do not differ from the types and frequency of adverse events reported in clinical trials.

The results of this study are intriguing and promising. Families of ASD patients, especially those with regressive autism, often find themselves, understandably, willing to try anything that may help without harming their child. You may encounter families who want to attempt to benefit GI and neuro-psycho-social pathology in their ASD child with FMT. It is essential that practitioners encountering these patients be familiar with techniques for facilitating safe home FMT using screened donors, or know how to properly refer the patient if not.

About the Author

Mark Davis, ND, is the medical director of Good Life Medicine Center, Portland, Oregon, and his naturopathic practice, Bright Medicine Clinic, focuses on gastroenterological health. Davis is one of a handful of physicians in North America with clinical expertise in fecal microbiota transplantation. Davis is on the board of directors of the Fecal Transplant Foundation, Carmel, Indiana, and chairs the Fecal Microbiota Transplant Committee for the C diff Foundation, New Port Richey, Florida. He received his naturopathic degree with honors in research from the National College of Natural Medicine, Portland. He cohosts the popular podcast The Naturocast.

References

  1. Sandler RH, Finegold SM, Bolte ER, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15(7):429–435.
  2. Goodman B. The rise of the do-it-yourself fecal transplant. WebMD. http://www.webmd.com/digestive-disorders/news/20151209/diy-fecal-transplant#1. Published December 9, 2015. Accessed July 26, 2017.
  3. Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol. 2010;8(5):471-473.