From the earliest days of this blog, I have talked about the too-often-ignored (and non-existent-in-most-people) macrobiome. Over the last few years, I’ve covered research papers that demonstrate over and over that helminths – intestinal worms, which are the predominant organisms of the mammalian macrobiome – are a potent stimulator of Th2 regulatory cytokines that modulate the inflammatory response.
In tidying up my desk today, I realized I have not yet told you about the one clinical trial done looking at the effects of helminths in autism spectrum disorders (ASD). This study was done several years back, but only just published.[i]
The justification for the trial lies in the fact that “Current literature supports a link between neuroinflammation, imbalanced immune responses, and ASD.” Researchers have found neuroinflammation in various parts of the autistic brain. Also, in animal models, maternal immune activation is known to result in autistic-like behaviors in offspring. Treating the pregnant animals with anti-inflammatory agents protects the babies, even when the mothers are immune activated. Thus, “…due to the inflammatory mechanisms implicated in the development and symptomatology of ASD, immunomodulatory interventions should be explored…”
An important side-note: Dr. William Parker, of Duke University Medical School, has also done research on this and shown that helminths are protective of babies. He used an animal model (rats) and the benign helminth, Hymenolepis diminuta cysticercoid: “We have demonstrated previously that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction…Here, we demonstrate that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths…completely prevented…cognitive dysfunction in adulthood.” By down-regulating the inflammatory response, helminths were able to protect babies’ brains from disrupted development, even when immune challenged.[ii]
After all (back to today’s paper): “The interaction of the developing immune system with microorganisms, including helminths, may be an important component of normal immune system maturation.”
As a proof of concept study, this clinical trial was small, only 10 higher functioning adults with autism. The scientists were simply looking to see how big an effect the helminths would have on repetitive behaviors, irritability and global functioning. They used TSO, Trichuris suis ova, which are whipworms native to pigs. They die in humans in about two weeks, and have “no known pathogenic potential.”
The test subjects were broken up into two groups, one receiving the TSO (2500 organisms every 2 weeks), one receiving the placebo. At the end of 12 weeks, each group went through a 4 week “wash out” period (during which they were given nothing), and then they were switched.
Considering that the 12 weeks on the helminths is not a particularly long time at all, the results were pretty darn remarkable.
“There were large effect sizes for TSO on rigidity and repetitive behaviors in ASD subjects…Multiple scales showed a significant percent change from baseline, indicating improvements in repetitive behaviors…Trending improvements were observed in irritability…”
As far as social communication, there was a small beneficial effect. I’m not sure how much improvement should have been expected in language in only 12 weeks.
The paper concludes with saying, “The potential impact of TSO vs. placebo in ASD is supported by moderate to large effect sizes….” and the authors of course suggest a future clinical trial, with a larger patient base. Good luck with that. Dr. Parker has been unsuccessfully trying to raise funds for helminth clinical trials for years. Considering that, as my regular readers know only too well, there is no treatment for autism, you would have thought this trial would have spurred huge action. Unfortunately (and tragically) not….
[i] Hollander, E, Uzunova, G, Taylor, BP, Noone, R, Racine, E, Doernberg, E, Freeman, K, Ferretti, CJ. Randomized crossover feasibility trial of helminthic Trichuris suis ova versus placebo for repetitive behaviors in adult autism spectrum disorder. World Journal of Biological Psychiatry. 2018 Nov 16:1-9. doi: 10.1080/15622975.2018.1523561.
[ii] Williamson, LL, McKenney, EA, Holzknecht, ZE, Belliveau, C, Rawls, JF, Poulton, S, Parker, W, Bilbo, SD. Got Worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. Brain, Behavior and Immunity. 2016: 51:14-28. doi: 10.1016/j.bbi.2015.07.006