Latest fecal transplant study: gut and autism symptoms improve after abx+fc treatement

[natasa778]

Autism symptoms improve after fecal transplant, small study finds

The study, which appears in the journal Microbiome, was conducted while Gregory and her adviser and co-author, Matthew Sullivan, were at the University of Arizona. Other lead researchers on the project are from Arizona State University and Northern Arizona University.

The researchers collected this information from parents through established, standardized questionnaires to assess social skills, irritability, hyperactivity, communication and other measures. One of those tools showed the average developmental age increased by 1.4 years after treatment.

...
The average score on a scale for ranking gastrointestinal symptoms dropped 82 percent from the beginning to the end of treatment. And when the researchers asked parents to give feedback on 17 autism-related symptoms, they saw overall improvement that was sustained two months after the final treatment.

The researchers also asked the children's doctors to complete a diagnostic evaluation before the experimental treatment, at the end of treatment and eight weeks after that. Those results pointed to lasting benefits.

...
Researchers also were able to document a rebalancing of the gut following treatment. At the end of the study, the bacterial diversity in the children with autism was indistinguishable from their healthy peers. The study also included a unique viral analysis by Ohio State scientists, made possible because of previous work in the world's oceans.

Gregory, who is particularly interested in the interplay between viruses and bacteria, used genetic testing to examine the viral diversity in the guts of the treated children. It rebounded quickly, and became more similar to the donor's microbiome.

"Those donor viruses seemed to help," she said.

== two weeks of antibiotics, followed by two weeks of high dose fc (SHGM formula), followed by seven-eight weeks low dose fc.

modified FMT protocol, termed Microbiota Transfer Therapy (MTT), involved 14 days of oral vancomycin treatment followed by 12–24 h fasting with bowel cleansing, then repopulating gut microbiota by administering a high initial dose of Standardized Human Gut Microbiota (SHGM) [37] either orally or rectally followed by daily, lower maintenance oral doses with a stomach acid suppressant for 7–8 weeks. A stomach-acid suppressant was used to increase the survival of SHGM through the stomach. Participants were followed for an additional 8 weeks after treatment ended, to determine if treatment effects were temporary or long-lasting.

Full paper here

 

[Murph]

I'd never heard of SHGM. It seems to be made from stool, but concentrated. Here's what the paper says.

>
Standardized human gut microbiota
Instead of pure stool, this study involved the use of standardized human gut microbiota that is > 99% bacteria and prepared as previously described using stool from healthy individuals as starting material [37]. Briefly, donors underwent rigorous screening that involved regular questionnaires, review of medical history, and physical examinations to rule out infectious disease, metabolic syndrome, gastrointestinal disorders, and neurologic or neurodevelopmental problems.

Serologic testing was performed to rule out infection with human immunodeficiency virus-1 and -2; hepatitis A, B, and C; and syphilis. The stool used in preparation was tested for potential bacterial pathogens (C. difficile toxin B, Campylobacter, Salmonella, toxin-producing Escherichia coli, Vibrio, Yersinia, Listeria, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus), potential parasites (Giardia, Cryptosporidium, Cyclospora, and Isospora), and potential viral infections (Rotavirus A, Adenovirus, and Norovirus). Metabolic health of donor individuals was assessed with physical examinations and serologic testing (fasting glucose, lipid panel, liver function tests, and high sensitivity C-reactive protein).

In addition, the fluorescent antinuclear antibody was employed as a screen for autoimmunity risk. Any single abnormality resulted in disqualification of the donor and prevents material release. The donated material was then extensively filtered and standardized under anaerobic conditions, following FDA good manufacturing processes (GMP), resulting in > 99% microbiota.

The final product was in liquid form which can be frozen and was proven to be highly effective for treating C. difficile [37]. The SHGM was stored in −80 °C freezers at Arizona State University (ASU), and then delivered to families on dry ice every week during the study. Families were instructed to keep the SHGM in a container with dry ice and thaw it shortly before use.

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As far as the paper goes, it looks awesome. Big effect size and high statistical significance despite the small sample size. Obvious implications for CFS. I'd try this in a heartbeat if it was offered.

 

[Cheesus]

This study seems to suffer from the core problem that we consistently criticise PACE for: it is an unblinded trial with subjective outcomes. Further to that, there was no control group, the sample size was very small and the follow-up was only two months.

I'd be delighted if more research could be done in this area for autism, as it seems to be an intriguing hypothesis. However this study is seriously lacking and we would not let it fly for one second if it were an ME trial of a psychological therapy.

 

[Murph]

Interesting point about the control group. There was a control group of sorts, but they were healthy and they didn't treat them. I guess patient collection was expensive and they wanted to make the sample size as big as possible? Maybe ethics committee questions too when dealing with kids?

I also wish they followed up for longer and I agree it's way too soon to make treatment recommendations based on this. I see studies like this as cheap preliminary ones that serve to guide future research, not treatment.

an unblinded trial with subjective outcomes.

That also more or less describes the Rituximab Phase II trial...

Also worth noting is that some sub-outcomes actually are objectively measured (microbiome diversity.)
and happily the paper calls at the end for a bigger, blinded trial! Which I'd love to see done.

 

[Cheesus]

@Murph

Yes, there were some objective outcomes. It was really the clinical symptoms I was referring to.

I think we can agree that we would both be happy for larger and more robust trials in this area.

 

[Sidereal]

Asking parents to rate their children's symptoms could beef up your results in the positive direction. Wishful thinking bias is just human nature I'm afraid. I think studies in this area should use blinded psych observers to rate behaviour. Not ideal either of course.

 

[Sidereal]

That also more or less describes the Rituximab Phase II trial...

Well, at least they used a placebo control (saline infusion).

 

[A.B.]

Again one ponders how a blinded trial of FMT would look like.

 

[AndyPR]

Again one ponders how a blinded trial of FMT would look like.

Unappetizing??