Studies help explain link between autism, severe infection during pregnancy

MIT News ^ | September 13, 2017 | Anne Trafton

[Enchante]

Mothers who experience an infection severe enough to require hospitalization during pregnancy are at higher risk of having a child with autism. Two new studies from MIT and the University of Massachusetts Medical School shed more light on this phenomenon and identify possible approaches to preventing it.

In research on mice, the researchers found that the composition of bacterial populations in the mother’s digestive tract can influence whether maternal infection leads to autistic-like behaviors in offspring. They also discovered the specific brain changes that produce these behaviors.

“We identified a very discrete brain region that seems to be modulating all the behaviors associated with this particular model of neurodevelopmental disorder,” says Gloria Choi, the Samuel A. Goldblith Career Development Assistant Professor of Brain and Cognitive Sciences and a member of MIT’s McGovern Institute for Brain Research. If further validated in human studies, the findings could offer a possible way to reduce the risk of autism, which would involve blocking the function of certain strains of bacteria found in the maternal gut, the researchers say. Choi and Jun Huh, formerly an assistant professor at UMass Medical School who is now a faculty member at Harvard Medical School, are the senior authors of both papers, which appear in Nature on Sept. 13. MIT postdoc Yeong Shin Yim is the first author of one paper, and UMass Medical School visiting scholars Sangdoo Kim and Hyunju Kim are the lead authors of the other.

Reversing symptoms

A 2010 study that included all children born in Denmark between 1980 and 2005 found that severe viral infections during the first trimester of pregnancy translated to a threefold risk for autism, and serious bacterial infections during the second trimester were linked with a 1.42-fold increase in risk. These infections included influenza, viral gastroenteritis, and severe urinary tract infections.

Similar effects have been described in mouse models of maternal inflammation, and in a 2016 Science paper, Choi and Huh found that a type of immune cells known as Th17 cells, and their effector molecule, called IL-17, are responsible for this effect in mice. IL-17 then interacts with receptors found on brain cells in the developing fetus, leading to irregularities that the researchers call “patches” in certain parts of the cortex.

In one of the new papers, the researchers set out to learn more about these patches and to determine if they were responsible for the behavioral abnormalities seen in those mice, which include repetitive behavior and impaired sociability.

The researchers found that the patches are most common in a part of the brain known as S1DZ. Part of the somatosensory cortex, this region is believed to be responsible for proprioception, or sensing where the body is in space. In these patches, populations of cells called interneurons, which express a protein called parvalbumin, are reduced. Interneurons are responsible for controlling the balance of excitation and inhibition in the brain, and the researchers found that the changes they found in the cortical patches were associated with overexcitement in S1DZ.

When the researchers restored normal levels of brain activity in this area, they were able to reverse the behavioral abnormalities. They were also able to induce the behaviors in otherwise normal mice by overstimulating neurons in S1DZ.

The researchers also discovered that S1DZ sends messages to two other brain regions: the temporal association area of the cortex and the striatum. When the researchers inhibited the neurons connected to the temporal association area, they were able to reverse the sociability deficits. When they inhibited the neurons connected to the striatum, they were able to halt the repetitive behaviors.

Microbial factors

In the second Nature paper, the researchers delved into some of the additional factors that influence whether or not a severe infection leads to autism. Not all mothers who experience severe infection end up having child with autism, and similarly not all the mice in the maternal inflammation model develop behavioral abnormalities. “This suggests that inflammation during pregnancy is just one of the factors. It needs to work with additional factors to lead all the way to that outcome,” Choi says. A key clue was that when immune systems in some of the pregnant mice were stimulated, they began producing IL-17 within a day. “Normally it takes three to five days, because IL-17 is produced by specialized immune cells and they require time to differentiate,” Huh says. “We thought that perhaps this cytokine is being produced not from differentiating immune cells, but rather from pre-existing immune cells.”

Previous studies in mice and humans have found populations of Th17 cells in the intestines of healthy individuals. These cells, which help to protect the host from harmful microbes, are thought to be produced after exposure to particular types of harmless bacteria that associate with the epithelium.

The researchers found that only the offspring of mice with one specific type of harmless bacteria, known as segmented filamentous bacteria, had behavioral abnormalities and cortical patches. When the researchers killed those bacteria with antibiotics, the mice produced normal offspring.

“This data strongly suggests that perhaps certain mothers who happen to carry these types of Th17 cell-inducing bacteria in their gut may be susceptible to this inflammation-induced condition,” Huh says. Humans can also carry strains of gut bacteria known to drive production of Th17 cells, and the researchers plan to investigate whether the presence of these bacteria is associated with autism.

Sarah Gaffen, a professor of rheumatology and clinical immunology at the University of Pittsburgh, says the study clearly demonstrates the link between IL-17 and the neurological effects seen in the mice offspring. “It’s rare for things to fit into such a clear model, where you can identify a single molecule that does what you predicted,” says Gaffen, who was not involved in the study.

The research was funded by the Simons Foundation Autism Research Initiative, the Simons Center for the Social Brain at MIT, the Howard Hughes Medical Institute, Robert Buxton, the National Research Foundation of Korea, the Searle Scholars Program, a Pew Scholarship for Biomedical Sciences, the Kenneth Rainin Foundation, the National Institutes of Health, and the Hock E. Tan and K. Lisa Yang Center for Autism Research.

[Enchante]

Fascinating research, seems to point to important linkages between maternal gut bacteria, the immune system, and possible development of autism in the child. Certainly merits a lot more attention....

[Enchante]

I wonder if this work can point to any possible research on therapeutic tools for kids who already have autism, or is the only hope here to try to address preventative measures during pregnancy?

For instance, could any medicine(s) be developed which would target the appropriate molecules in the brain? Probably a long way away still, but maybe hopeful....

[DoughtyOne]

Thanks so much for your support to this point... I personally apprecaite it...
FReepers, it's far beyond time to wrap up this FReep-a-thon.  Lets do it today.  Please chip in.

President Donald J. Trump and the Free Republic of the United States of America
President Donald J. Trump's address to the United Nations on 09/19/2017.

Ramirez political cartoon:  Sanctuary State LARGE VERSION 09/21/2017: LINK  LINK to regular sized versions of his political cartoons (archive).
Garrison political cartoon:  Good Boy LARGE VERSION 09/21/2017: LINK  LINK (scroll down) to regular sized versions of his political cartoons (archive).


Please join the monthlies, an automated and the best way to help support Free Republic.  If you opt not to join the automated monthly support program, please consider joining the One One Done project.  LINK

FReepers, 98.21% of the Third Quarter FReep-a-thon goal has been met.  Click above and pencil in your donation now.  Please folks, lets end this FReepathon.  Thank you!
...this is a general all-purpose message, and should not be seen as targeting any individual I am responding to...

Just $694.00 dollars to 99.00%

[exDemMom]

I still think autism is a result of a combination of environmental and genetic factors. Plenty of women get sick during pregnancy and give birth to perfectly healthy infants. I wonder if there could be variants in the IL-17 receptors in the brain that make them particularly susceptible to damage.

I’ve also seen where some studies link higher rates of autism to febrile illness in the mother. Although it could be that febrile illnesses induce higher levels of IL-17 or other cytokines which are responsible for the damage.

This is fascinating stuff, and so very important. Because once the cause(s) of autism are described, that removes a huge talking point of the anti-vax (anti-baby) fraudsters. Plus, it opens doors to prevention—possibly treatment, but that’s a lot harder.

[logi_cal869]

I have been doing battle with pro-vaccination sycophants - the same ones who consider vaccines sacrosanct and label ALL those who criticize vaccines as “anti-vaxxers” - for some time. It is an irony that so many educated & normally-intelligent people would hysterically-defend all vaccines while ignoring other factors, including both adjuvants and biological factors themselves.

That stated, modern medicine has NO KNOWLEDGE whatsoever of the gut and, in fact, has no medical name for the condition from which I recovered.

This research is no doubt interesting, but for me it’s a face-palm moment that no researcher ever considered the linkage between vaccines and negative reactions from the heart of our immune system: The gut.

[Nifster]

Oh the anti vaxers won’t like that

[logi_cal869]

It would be a mistake to deride those who go to the extreme of becoming anti-vaccine, aka the euphemism beloved by vaccine sycophants, “anti-vaxxer.”

I know far too many people who have children with autism, Asperger and other disabilities. If modern medicine was not so intransigent, people wouldn’t become anti-vaccine to protect their children.

Vaccines are not sacrosanct; vaccine safety should be positive-feedback, not ignorant and defensive in the face of harm perpetrated upon children as a result of failure to make vaccines and their application safe for the mother and their offspring.

The simple fact of the matter is that many vaccines use chemicals & compounds which can be easily linked to biological reactions, yet they continue to be used.

For decades those critiquing vaccines and their sycophant defenders claimed that ethyl mercury was safe when injected into the bloodstream, on face value a laughable position from anyone who understands the elements. Not only did the establishment finally overcome the powerful lobby which persisted in using thimerosal, research has finally been performed which demonstrates toxicity resulting from ethyl mercury.

My response: Duh.

This research could be (emphasis on “could”) a sign of a trend, but the pressure to move to single-payer will quash all such research and destroy any remaining integrity in medicine & medical research.

Those who are considering having children in the coming years have genuine reason to be concerned, as it is best analogous to Russian Roulette whether you’re going to have a healthy child, given statistics on pre-term births and all the other unknowns.

Again, the ratio of affected children I know personally is quite troubling.

One observation: The “environmental factors” you refer to include “choices” by the mother. I’ve make the case in my book that mothers should be proactive in planning for pregnancy for up to 2 years prior to consideration of going full-term, as the one aspect medical research totally-ignores is rather academic: Mother’s health. People are far too quick to jump on the “new drug” or “gene therapy” bandwagon when basic health is likely the order of the day...

[Nifster]

You just keep doing you boo

[mad_as_he$$]

After many years of observation I am convinced that gut bacteria is/are critical in having a healthy body. This will be the next big medical field of new discoveries.

[logi_cal869]

Say what?

[mewzilla]

And if a pregnant mom catching the flu, for example, increases the risk of having an autistic child, seems to me that makes another great case for vaccination. Not to mention staying home when you’re sick, for example, with something like viral gastroenteritis. Why put others at risk?

[Mr Ramsbotham]

The simple fact of the matter is that many vaccines use chemicals & compounds which can be easily linked to biological reactions, yet they continue to be used.

It's not just chemicals and compounds that should cause concern, but rather, the action of the antigens on the immune system, which can be diverted and left vulnerable to other agencies. Vaccination should be used judiciously. Just as bad as the "anti-vaccination" mentality is the "pro-vaccination" counterpart that considers any vaccination, in any combination, at any time and under any circumstances is beneficial. The veterinary profession (to its great cost, for vaccination is the mainstay of its practitioners' incomes) has adjusted its recommended vaccination protocols for dogs and cats after concluding that many adverse conditions can be caused by over-vaccination, including autoimmune conditions and cancers.

[Gay State Conservative]

Vaccines are not sacrosanct; vaccine safety should be positive-feedback, not ignorant and defensive in the face of harm perpetrated upon children as a result of failure to make vaccines and their application safe for the mother and their offspring.

Thanks for the bit of educated wisdom.Now would you like to explain how WTC7 was deliberately brought down by explosives planted in the basement?

[logi_cal869]

Exactly, top to bottom, except your comment, “vaccination should be used judiciously.”

In the absence of balancing safety, it becomes reckless...rebounding back to your other which echoes my assertion that pro-vaxxers’ histrionics are as bad as the others.

The thimerosal debacle is evidence that without changes in the discipline itself, it may be decades before basic ethics returns to medical research and ensures vaccine safety.

[logi_cal869]

You spew just like the liberal idiots I do battle with daily.

A little conflicted, are we?

[Gay State Conservative]

You spew just like the liberal idiots I do battle with daily.

I have 25+ years experience at Harvard Medical School.What does your CV look like?

[logi_cal869]

It’s good that you admit your conflict of interest.

But I have a question, oh wise one:

How many of the top 10 leading causes of death has medicine identified a cause?

Your ‘discipline’s’ intransigence is that which has delivered this country an epidemic of disease, autism among them.

I guaran-damn-tee you that I have a better understanding of the linkage than you.

[Gay State Conservative]

It’s good that you admit your conflict of interest.

OH,God...gimme a break.

C'mon now...tell us how Bush and Cheney personally planted hi tech explosives in the basement of WTC 7.The world has a right to know!

[Southside_Chicago_Republican]

Bookmark

[Gay State Conservative]

I guaran-damn-tee you that I have a better understanding of the linkage than you.

Your CV...we're still waiting!