By Teresa Conrick
In late Spring, this study came out, Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice . The importance of the results should jolt even the most skeptic:
“We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors.”
Some were not happy with that conclusion. It may be that as we find more concrete evidence that it is the microbiome and NOT genes as the epicenter of autism, ---money, causation, and reputations--- may be challenged. Because my daughter has been so affected, my perseveration of the microbiome for these many years has indeed, been the right path. Searching for answers to improve the health and well-being of increasing numbers of children on the spectrum, is a huge motivator for many of us. Let’s take a look at what this all means.
The impressive list of researchers is outstanding . Many have researched autism and all of them seem to be well acquainted with the microbiome. Their expertise in Biology, Biological Engineering, Microbiology, Environmental Biotechnology, Neurology, Biomedical Science, Genome Sciences, Neurobehavioral Genetics, and Microbiome Innovation shows the encompassing knowledge that powered this research. What is more astounding is that this study can now be added into the increasing list diagnoses. If you transplant gut microbiota from human donors with or TD controls into germ-free mice that colonization with microbiota is sufficient to induce. That list thus far:
- Schizophrenia - “The most intriguing evidence came when the researchers gave germ-free mice fecal transplants from the schizophrenic patients. They found that “the mice behaved in a way that is reminiscent of the behavior of people with schizophrenia,”
- Irritable Bowel Syndrome (IBS) and anxiety - “mice colonized with bacteria from IBS patients with anxiety symptoms showed similar symptoms in both behavioral tests. Those mice colonized with gut bacteria from IBS patients also displayed signs of immune activation associated with low-grade inflammation compared to mice colonized with bacteria from healthy individuals…”
- Parkinson’s Disease - “microbiota transplant from PD patients to αSyn-overexpressing mice and observed an enhancement of physical impairments compared to microbiota transplants from healthy human donors. The findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD4. “
- Multiple Sclerosis - “microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls.”
- Depression - “Fecal microbiota transplantation of GF mice with ‘depression microbiota’ derived from MDD patients resulted in depression-like behaviors compared with colonization with ‘healthy microbiota’ derived from healthy control individuals.”
All of those studies you see above, have families and researchers hopeful and motivated to continue more studies, with the ultimate goal of treatments, medications and cures, to help so many ill people. Yet, AUTISM, the youngest hit group affected by microbiome dysfunction, with all of its subsequent medical and behavioral issues, constantly has to deal with controversy. Now, it’s about this study above, and Spectrum, a site funded by the Simons Foundation Autism Research Initiative (SFARI) , where it appears that the focus is solely on genetics , had this to say: “ Study of microbiome’s importance in autism triggers swift backlash” :
Many scientists have pointed out possible errors of analysis and interpretation in a high-profile study that suggested microbes can ease autism-like behaviors in mice….Minutes after the study was published, independent experts began raising concerns on Twitter about three graphs included in the paper.
Given the very high number of variables being probed, it's not surprising some differences are found. No replication samples are tested, so my prior expectation would be that these are spurious, until proven otherwise
Wiring the Brain is all about -- “how the brain wires itself up during development, how the end result can vary in different people and what happens when it goes wrong “ -- and there are 0 articles on the microbiome and the focus on autism is pretty much about genes.
Other examples: “The data didn’t pass what I call the eyeball test,” one of the tweeters, Kevin Mitchell, associate professor of genetics at Trinity College Dublin in Ireland, told Spectrum…….“ and a tweet from another genes-only lab, “The Sebat laboratory is interested in understanding the molecular basis of neuropsychiatric disorders including schizophrenia, bipolar disorder and autism. We are interested in the role of copy number variants (CNVs) in disease…...
Don't even get me started on the N of 3 controls and 5 cases that were used for most analyses. The variability between donors was huge.
The researchers stand by their original results: “As we sit here today, we’ve found no errors with the statistics we’ve done,” Mazmanian, professor of microbiology at the California Institute of Technology in Pasadena, told Spectrum.
This additionally significant part of their study could be seen as another nail in the coffin of those doing exclusive gene research as the cause of autism:
The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
This is not the first study about autism to be attacked. Funding for autism research started with psychiatry back in the 1930’s until the study of genetics became more popular. Millions of dollars have been spent and wasted on searching for autism genes, with absolutely no benefit to society or more importantly, the affected individuals and their families. Moving autism into it’s more appropriate medical domain, a gut-brain disease for many, with a spectrum of immune dysfunction and behavioral symptoms, has been no easy feat and again, I applaud those researchers who are doing it.
The Very Real Hope
There are many fans of these gut-brain studies, including me. Smithsonian had this recent, well-done article, discussing the details of this pertinent, research and hopeful treatments:
The microbiome—a collection of organisms including bacteria, archaea, fungi and viruses that live in the human gut—has been shown to play a significant role in brain function. ……."There is a very high correlation between [gastrointestinal] severity and autism severity—for language, for social interaction, for behavior, all of the core symptoms of autism,” says Jim Adams, a professor and autism researcher at Arizona State University…..
Mazmanian and a team of researchers demonstrated this gut-brain connection in a mouse model of autism in 2013. Three years later, the team did the same for Parkinson's disease. And recently they showed that transplanting feces from a person with autism into germ-free mice would produce many symptoms of ASD in the animals.
The article really accentuates their work and shows the benefits of the research for individuals.
It will take time and multiple studies to answer these questions, but Adams is optimistic that a licensed microbial treatment for ASD will become available in a few years...If medical researchers like the ASU team can continue to make progress developing a microbiome treatment for ASD, many more kids could benefit from the multifold value of a healthy gut.
Megan is 26, and grateful is the word that always comes to my mind when I read these studies and see the huge impact it has on the future of autism for so many. We have been waiting too long.
Teresa Conrick is Science Editor for Age of Autism.