For a few years now, Rosa Krajmalnik-Brown from ASU has been researching whether the microbiota are implicated in autism spectrum disorder, either by affecting a range of measurable behavioural characteristics of ASD or by affecting the gastro-intestinal discomfort that often accompanies ASD and where the severity of GI complications mirrors the severity of ASD symptomatology. A paper published online today in the journal Microbiome reports on a small study, together with collaborators from Northern Arizona University, Ohio State University, and the University of Minnesota, on the effectiveness of regular microbiome transplants into children with autism spectrum disorder. And there are linked Eurekalert press releases from ASU and OSU. On an admittedly small sample group of 18 people aged 7 to 16 years old with ASD they demonstrated an average 80 percent improvement of gastrointestinal symptoms associated with autism spectrum disorders and 20-25 percent improvement in autism behaviors, including improved social skills and better sleep habits, among improvements in other measures of autism-related behaviour as tested on a recognised scale.
Volunteers were first treated with vancomycin to suppress any resident pathogenic bacteria. Bowels were then flushed with a product called MoviPrep and the children and their parents offered either a rectal route or an oral route to replenish gut bacteria. Those who elected for an oral route were given a proton pump inhibitor to suppress stomach acid. After initial high doses, via each route, introduction of transplant material was maintained for 8 weeks with smaller daily doses. The team report a big increase in microbe diversity and a big increase in certain bacteria, especially Prevotella, which they had previously found was low in children with autism spectrum disorders. There was evidence that the transplants had engrafted, at least partially, to the recipients.
The study authors freely admit that this is a preliminary open-label trial with a low number of subjects. As such there was no control for possible placebo affects nor were the investigators blinded. Neither was the trial randomized. Furthermore, it was only capable of investigating the combined outcome of antibiotic, antacid, bowel flush and fecal or oral microbiome transplant – they were unable to tease out what separate affect could be attributed to each of these treatment factors. The results, they say, should therefore be treated with caution and there is a need for further trials using larger numbers, a longer follow up time, better clinical determination of increase or decrease in symptoms with less reliance on parental report, and a statistical teasing out of all variables. Nevertheless they conclude that it presents evidence that microbial transplantation is safe and well-tolerated in children with ASD ages 7–16 years and that it led to significant improvements in both GI- and ASD-related symptoms which were sustained at least 8 weeks after treatment. Coincident with these clinical improvements, they say, both microbiota and phage from the donors appear to have engrafted, at least partially, in the recipients. This shifted gut microbiota of children with ASD toward that of neurotypical children, they maintain, is consistent with the hypothesis that gut microbiota may be at least partially responsible for GI and ASD symptoms.
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Is the evidence hardening for implicating the gut microbiota in either or both the cognitive and gastrointestinal symptoms associated with autism spectrum disorder? In this very recent editorial in the journal Cellular and Molecular Gastroenterology and Hepatology, Jonathan Braun, of the David Geffen School of Medicine at UCLA, reports very favourably on a paper in the same issue by Luna et al, which, he says, stands out from the crowd in these “wild frontier days of microbiota research” where too many studies lack controls, or large numbers, or sophisticated detailed techniques to explore either microbiome genomics or metabolites. As he says: “Several strengths in design and analysis distinguish this study. First, its care in patient phenotypic selection (gastrointestinal dysfunction and stratification of the pain subset) and bio- specimen choice (mucosal biopsy vs fecal) ensure that the collected data are closest to the clinical state and biologic site in question. Second, deep 16S metagenomic sequencing and optimized pre-analytic bioinformatics permit resolution of microbial taxa not previously reached by prior studies. Third and most exciting is the simultaneous assessment of the mucosal ecosystem in single biopsies, including microbial composition and bioamine and cytokine production. Such simultaneous measurement permits the follow- through with powerful bioinformatic analyses to construct potential functional relationships between microbiota and clinical relevant properties of the mucosal site.” Key findings of the research involve the role of the microbiome in production of the cytokines interleukin 6 and interleukin 17A and serotonin. Their work only relates to the gastrointestinal inflammation, very like IBD, that frequently accompanies the behavioural/cognitive symptoms of autism.