Transplanting Human Autism Microbiome In Mice Causes Autism
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 Study
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.”
The Controversy
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:
How the Gut Microbiome Could Provide a New Tool to Treat Autism
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.
Many genetic variants have been linked to autism, but only a handful are potent enough to induce the disorder on their own. Among these variants, mutations in a gene called Shank3 are among the most common. While mutations in these genes are generally rare, Zinc deficiency via interactions with the proteins encoded by these genes also leads to the development of autism and links different environmental to genetic causes. The protein encoded by the Shank3 gene is regulated by Zinc - Zinc shapes the properties of developing synapses via Shank proteins. See the copper/zinc section of my ongoing autism research I'm putting together, still in development. https://tgl.ink/v0VrgZ
Lactobacillus reuteri, which is commonly found in human breast milk, promotes social behavior via the vagus nerve, which bidirectionally connects the gut and the brain. When the vagus nerve is active, it releases oxytocin, a hormone that promotes social interaction. Oxytocin is released into the reward areas of the brain where it binds to molecules called oxytocin receptors, triggering social reward. We found that when the vagus nerve connecting the brain and the gut was severed, L. reuteri could not restore social behavior in ASD mice. The scientists tried another Lactobacillus species that was also reduced in the offspring (L. johnsonii) but that did not change social behaviors. The effects of L. reuteri on social behavior are not mediated by restoring the composition of the host’s gut microbiome, which is altered in all of these ASD models. Instead, L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice. OXTR inhibition prevents L. reuteri’s effects on social behavior and VTA plasticity. L. reuteri reversed social deficits even in germ-free mice.
We have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 Knockout (KO) mice. Lactobacillus reuteri, a gut bacterial species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. Therefore, L. reuteri treatment has a sex-dependent effect on social behavior, and sex-independent effects on repetitive behaviors in Shank3 KO mice. In addition, L. reuteri treatment modifies GABA receptor gene expression and oxytocin expression in Shank3 knockout mice. We further tested if Shank3 KO mice display dysregulation in the immune response by testing the plasma levels of six key immune markers. All of the immune markers were dysregulated in both male and female Shank3 KO mice compared to WT. Of even greater interest, while three of these molecules displayed the same dysregulation among male and female mice, three of them actually displayed the opposite dysregulation among males and females. IL-10 and IFNγ increased in Shank3 mice of both sexes, while IL-1b decreased in Shank3 KO mice of both sexes. In contrast, IL-17a and TNF-a increased in male Shank3 KO mice, while they decreased in female Shank3 KO mice. To test if L. reuteri can induce changes in the immune response, we tested levels of plasma immune markers in Shank3 KO male mice after L. reuteri administration. L. reuteri administration increased all tested markers, except for the reduction of IL-17a plasma levels. IL-17a has recently been implicated as a central factor in maternal immune activation-induced autism phenotype.
Posted by: David L | September 16, 2019 at 06:08 PM
An Atkins diet of 15 carbs or less.
Or stop eating early and fast through the night, and eat low carb until the evening meal.
or do the keto diet, and add in that diet plenty of MCT oil
Posted by: for Otto | September 14, 2019 at 12:10 PM
Otto, since most bacteria do best on carbs, lower your carbs. Do it by diet for now.
Posted by: Benedetta | September 14, 2019 at 12:06 PM
How can i cultivate Prevotella Histicola bacteria in my body? Where can i obtain?
Posted by: Otto | September 13, 2019 at 12:21 PM
Carol:
Our dearest Tom Insel, and some scientist called Crawley says they are flinching mice that they call schizo.
Here is the article:
https://www.npr.org/templates/story/story.php?storyId=1178800
Posted by: Benedetta | September 10, 2019 at 05:29 PM
In the USA, white people consume twice as many antibiotics as Hispanic people and also have twice the rate of Autism. Is there any other variable that correlates so closely?
The confusion probably arises because not all antibiotics are equally damaging. The main ones probably causing most of the horror are the fluoroquinolones like Cipro, which have caused so much carnage there are multiple groups of up to 10,000 people on Facebook calling themselves 'floxies' from the fluoroquinolone toxicity. And the FDA finally gave the life altering syndrome a name, Fluoroquinolone Associated Disability, or FQAD, which includes neurological disorders.
Cipro was one of the top selling antibiotics in the USA for many years. It has probably caused massive damage. The running theory among the floxies (I'm one myself), who have spent the years after being 'floxed' learning everything possible about it, is that the mitochondrial DNA has been damaged because FQs are designed to target the DNA of single cell organisms, and mitochondria are essentially just that, living in our cells in a symbiotic relationship.
Mitochondrial DNA (mtDNA) is passed from parents to child, so if the parents have been floxed, then the child can theoretically inherit those damaged mtDNA. Damage to the mtDNA causes all kinds of syndromes, from chronic fatigue to autoimmune disorder.
The FQs no doubt damage a lot of the good microbes in the gut, so they basically hit us on every level. So we're all looking for one thing or another, when it's probably all of the above, with the main source being the FQs.
My opinion.
Posted by: Greg | September 10, 2019 at 02:26 AM
These self-appointed guardians of the scientific gates are afraid to watch their genes-only specializations dry up as they’re forced into less-glamorous realms, such as the gastrointestinal system.
**********
My first meeting with our son's DAN doctor was back in 2007. And one of the first things he said to me was:
"So you're familiar with the song lyric 'shin-bone is connected to the knee-bone'? Yeah, well good. Because now you need to learn about how the 'gut-bone is connected to the brain-bone'"
Doctors know exactly what's going on. The difference between DAN doctors, and most other doctors, is that DAN doctors have the courage to face this truth. And to use their understanding of it, to try and help some of these vaccine injured children.
The genetics excuse is just another scheme that was devised to blame the victims. And allow the conscienceless doctors to walk away scott free.
Posted by: Barry | September 09, 2019 at 11:13 PM
Many thanks Teresa always great to read your articles.I know that if we keep our sons diet clean,as possible his behaviours manic stimming etc decrease.The lad who used to go round the tops of skirting boards with his finger trying to find gluten when his diet was completely clean and he was suffering withdrawal from gluten.These days he doesn't bother unless hes just got flyer and were missing something..as we get older we see less but we all seen the gut brain link many many moons ago and Dr Wakefield was the first to remind them all of that,the gut brain behaviours happen in autism also.
Pharma For Prison
MMR RIP
Posted by: Angus Files | September 09, 2019 at 04:17 PM
Some researchers hoard scientific uncertainty like currency, to leverage for personal ambition, buying time, building power, amassing a fortune. Their inaction is abetted by medical corporations and parasitic foundations that collect donations ostensibly to halt disorders like Parkinson’s and MS.
These self-appointed guardians of the scientific gates are afraid to watch their genes-only specializations dry up as they’re forced into less-glamorous realms, such as the gastrointestinal system.
All this self-serving stonewalling comes at the expense of people struggling with vaccine-induced autism, plus their parents and relatives suffering from autoimmune disorders who’ve shared information on it in online forums for 15 to 20 years or more. What a tragic and unnecessary waste.
Posted by: nhokkanen | September 09, 2019 at 02:42 PM
George Mead
Yes, I remember Andy Wakefield up against a paediatric psychiatrist from Great Ormond Street Hospital c.2000 at an Imperial College Conference. The psychiatrist maintained that the gut could not affect the brain. AW used two examples (1) a glass of beer (2) psychiatric medicines...
Posted by: John Stone | September 09, 2019 at 02:17 PM
What never ceases to amaze me is the fact that the gut-brain connection has been well understood on one level for literally millennia, at least as long as humans have known how to make alcoholic beverages. Yet our medical establishment's first line of "treatment" for behavioral issues is psychiatric! I began subscribing to Berni Rimland's newsletter about 20 years ago. Around that time my partner began exhibiting intermittent periods of bizarre behavior. She received standard medical care, at one point taking around twenty psych meds. Finally, she was correctly diagnosed with hepatic encephalopthy, secondary to cirrosis. When correctly treated her psychiatric symptoms disappeared. The transplant team immediately ordered the cessation of ALL drugs that required clearance through the liver, but of course, it was far too late by then...
Posted by: George Mead | September 09, 2019 at 01:52 PM
Fecal transplants?
Change of diet?
Mercola website suggest that you eat early suppers in the afternoon, then when you wake up try to prolong the Keto - no carb metabolism as long as possible. You can do that by not eating, or eating a breakfast very low in carbohydrates.
Dogs are fat, so this research project changed the dogs' diets to more protein and less carbs.
https://phys.org/news/2017-01-dog-diet-gut-microbiome.html
Another study showed dogs with IBS, will improve with change of diet. This paper discusses not only does the microbiome makes serotonin, and puts the methyl groups (CH3) on B vitamins so our bodies can better use those B vitamins; they also found in this study that certain microbiome can make bile. So it is just not the dogs gall bladders alone.
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0740-4
That last study says that dogs microbiome is pretty similar to humans. That makes sense, since dogs have been around humans for a really long time; eating our table scraps and all.
Then Jesus said for those with epilepsy/ having fits , that all should fast and pray which was what the ancient, famous, Roman physicians were saying at the time too.
The modified Atkins diet, of around 15 carbs a day, the Cleveland Clinic research group said would help reduce seizure, and even heal "stop for good" seizures.
A brain injury will mess up the motility of the gut. If you live, a brain injury will heal, maybe, or maybe not returning to full normal function, but that gut microbiome that got messed because of motility problems might need help.
I guess we are all waiting for Dr. Mike Adams of the University of Arizona to patten his really healthy, sure enough from a healthy humans gut pills. How are we to get the rest of the protocol in place I wonder.
Will they send out letters to all the doctors to let them know that they are allowed to o put some of us on their prescious antibiotics, and over the counter acid reducers along with these healthy human fecal pills? Will they make the those healthy, human, fecal pills prescription or over the counter? I would like to know where these healthy humans came from? A miracle for sure.
Another question is how much will a good microbiome be able to over come?
Will it again allow some one to eat gluten? I am not sure gluten (wheat) is a health food and we as humans might have to start rethinking of this staple "the bread of life" as ? What? Junk food? And what about things like sugar? I am pretty sure that both those foods fit really well into our own ophoid receptors of our body.
But change of diet, I wonder, can it heal schizo ?
Now that these virgin micro free mice have been contaminated with microbes that gives them trouble what is the best way to make them healthy?
Posted by: Benedetta | September 09, 2019 at 01:15 PM
I bet that in the long run -- and this might take another 20 years -- Andrew Wakefield will be awarded a Nobel Prize for being the first to notice and report the role played by gut health on brain health. At the same time somebody like Stephanie Seneff and Anthony Samsel should awarded prizes for their elucidation of the role that environmental toxins, like the glyphosate in our food, play in disrupting the gut microbiome. I imagine that there is also already some prize-worthy Big Pharma-threatening research on the role that the over use of antibiotics -- both as prescriptions (e.g. for treating ear infections) and in our food supply -- play in disrupting our microbiome. I'm still relatively new to all this stuff so I don't know yet -- maybe some other contributor to this web site does know and will be kind enough to point me to some relevant research -- exactly how vaccines play a significant role in disrupting the gut microbiome. I'm guessing that it is by disrupting the entire natural immune system, something like 70% of which appears to be located in the gut. That, too, would seem worthy of yet another Nobel Prize.
Posted by: Greg Hill | September 09, 2019 at 12:59 PM
I'm curious what behavior in a mouse would be considered schizophrenic. I had a schizophrenic relative who seemed almost normal much of the time, but at others would wander around the house in a nightgown and end up standing in a corner talking to invisible people.
Posted by: Carol | September 09, 2019 at 10:54 AM
Thanks, Teresa. A fascinating and promising field of inquiry. Attacked, of course, by those with more hubris than curiosity.
Posted by: Gary Ogden | September 09, 2019 at 08:34 AM
Incredible !
Posted by: Hans Litten | September 09, 2019 at 06:12 AM