TACA Reflections: Autism and My Research Heroes

As I started typing this post last night, I was sitting in Los Angeles airport awaiting my very delayed flight home.  I was at the national TACA (Talk About Curing Autism) Conference, which is always a truly wonderful experience.

The Conference boasted a top quality line up of doctors and researchers this year, including a really very touching and funny keynote speech by Erin Brockovich.

The two highlights of the conference for me:

  1. Seeing a talk by Dr. Robert Naviaux on his small-but-remarkable trial using Surinam in autism.  If you have a child on the  spectrum, take the time to read  about this.  In my nearly 22 years in autism, it is one of the most promising lines of research I have ever seen.
  2. I actually got to talk, for quite some time, with Dr. Derrick MacFabe, who my regular readers know is one of my favorite researchers ever. (I managed, just barely, to keep from giggling like a 12 year old meeting Justin Bieber and asking for his autograph.)  MacFabe’s work on microbiome alterations in autism is truly among the most important research done in the last 2 decades.  And it’s not just me who says so, by the way.  Two years ago, the Nobel Forum Symposium, in Sweden, invited him and 9 other researchers to speak at a small meeting on microbiome research.

Coincidentally, or perhaps not now that I think of it…my post of March 30th of this year described a paper by Drs. MacFabe, Frye, Kahler and Slattery that explores the 3 most promising lines of research in autism at the moment:  the work of Dr. Naviaux and the cell danger hypothesis; proprionic acid issues, such as Dr. MacFabe has been researching for the last couple of decades; and finally – biome depletion, and the use of helminths to restore the biome.

At one point, I commented to another mother that Dr. Naviaux’s work was the most exciting thing I’ve seen in autism in years.  She corrected me – his work and helminths.

Thanks to people like Dr. MacFabe, Dr. Frye, Dr. Naviaux, and a few others., perhaps finally some meaningful progress is actually being made in autism.

 

 

And yet MORE on the Yeast/IBD Connection

Back in September, I wrote about a summary I’d stumbled across describing the current state of research into the connection between the mycobiome and inflammatory bowel disease.  Then, just a few days ago, I put up a link [i]on my Biome Buzz Facebook page about the connection between alterations in the mycobiome and obesity.  (Briefly: mice fed a high fat diet had higher levels of Candida albicans in their guts than controls as well as alterations in the bacterial microbiome.)

Then today, I found out about research[ii] that came out earlier this month, examining other phenomena in the IBD/fungi connection.  Apparently, people with IBD are known to have higher levels of the fungi Candida tropicalis well as the bacterial species, E. coli and Serratia marcescens.  When grown separately in lab dishes, these 3 species form colonies but when mixed, they grow out of control and form large and robust biofilms.  (Biofilms are “structured microbial communities that shield bacteria from antibiotics.”)

In the presence of these two species of bacteria, C. tropicalis stretches out into long filaments to which E.coli fuses.  In the meantime, the S. marcescens forms protein strings that stabilize the growing biofilm.  “Their partnership allows them to outcompete loner bacteria and fungi.”  More than that, these biofilms cause intestinal inflammation.

The researchers propose that giving those with Crohn’s disease antifungal drugs and then adding in beneficial fungi could create a heather microbiome.

Says one of the scientists, “To get the whole picture…we’re going to need to start looking at the mycobiome in addition to the microbiome.”

Yeah – and the virome and macrobiome too!

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[i] https://www.sciencedaily.com/releases/2017/10/171011131654.htm

[ii] https://www.sciencenews.org/article/gut-fungi-might-be-linked-obesity-and-inflammatory-bowel-disorders

BPA, the Microbiome and Chronic Illness

This week I posted an article on the Biome Buzz Facebook page about Australian research that suggests that the more inflammation present in the mother, the more socially impaired her child with autism.[i]  This, after last week’s post about how something in the maternal bacterial microbiome leads to a maternal infection affecting her baby’s brain development.  Then yesterday I read about an article just published in the American Society for Microbiology’s journal, mSystems, that shows that  (in rabbits – and presumably humans) exposure to the  toxic chemical, BPA (which is added to many products, including plastic food containers) just before or after birth reduces bacterial microbiome diversity and subsequently, bacterial metabolites, including anti-inflammatory short-chain fatty acids.  Exposure to BPA also led to an increase in the toxic bacterial by-product, lipopolysaccharides, which is highly pro-inflammatory.[ii] (In fact, when researchers want to induce inflammatory bowel disease, for example, in animal experiments, they inject them with lipopolysaccharides.)  Thus, BPA exposure may well set the infant up for chronic inflammatory disease going forward.

Back last April, I wrote a post called Alex and Autism: His Perfect Storm.   I’ll need to update that at some point, and add the above factors.  I already mentioned, in that post, that “I already had a long history of immune issues myself and then got the flu.” Now, to boot,  once I was told to stop breast feeding him when he was a few days old, I dumped his soy-based formula into BPA-laden plastic baby bottles.  The FDA did not ban BPA in bottles and cups until July of 2012. (Alex was born in 1994.) As though all this weren’t enough…what has put me into one of my moods, having just read a New York Times’ article about this ban,  was that actually, the FDA apparently still regarded BPA as safe.  In the article, an FDA spokesman is quoted as saying that “…the decision did not amount to a reversal of the agency’s position on the chemical.  The FDA declared BPA safe in 2008, but began expressing concerns about possible health risks in 2010.”  It goes on to say that, “Michael Taylor, deputy commissioner for foods at the agency, said the decision simply codified what the industry was already doing based on the preference of consumers and did not reflect concerns about the safety of BPA in baby bottles or toddler’s cups.”[iii]

Wait…WHAT?!  The FDA had concerns about BPA in 2010, but was only banning the substance in infant bottles and cups to mollify consumers?!  What am I not getting here?

Is it me?

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[i] https://www.sciencedaily.com/releases/2017/10/171010133907.htm

[ii] Lavanya Reddivari, D. N. Rao Veeramachaneni, William A. Walters, Catherine Lozupone, Jennifer Palmer, M. K. Kurundu Hewage, Rohil Bhatnagar, Amnon Amir, Mary J. Kennett, Rob Knight, Jairam K. P. Vanamala. Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites. mSystems, 2017; 2 (5): e00093-17 DOI: 10.1128/mSystems.00093-17

[iii] http://www.nytimes.com/2012/07/18/science/fda-bans-bpa-from-baby-bottles-and-sippy-cups.html

Maternal Infection, Autism and the Bacterial Microbiome

I posted a news story about the latest autism/microbiome findings a couple of weeks ago, but saw this article[i] today in Spectrum magazine and thought it worth writing about as it really is important research.  I’m sure too it has implications beyond autism.

Ultimately – from 4 major pieces of research – we now know how maternal immune activation may lead to autism in children.  (We already knew, from epidemiological studies, that autism risk increases by 37% in cases of maternal infection.)

  1. In 2014, a study showed that children with autism have patches of immature neurons in the cortex of their brains.
  2. In 2016, researchers found this same “anatomical oddity” in mouse pups who’d been exposed to infections while in utero.
  3. The latest study shows that these neurons are over-active, potentially causing autism-like behaviors in the mice. (This confirms too one of the main theories of autism:  “…too much excitation in brain signals relative to inhibition.”)
  4. A 2nd paper, in the same issue of Nature, showed that these brain patches and subsequent behavioral problems could be prevented by giving the pregnant mice vancomycin, an antibiotic.

“This finding implicates gut bacteria in the effects of maternal inflammation on the developing brain.”

HOLY COW.

More on #3 above:  Pregnant mice were essentially infected with a virus. The researchers then measured the amount of time their pups spent burying marbles and interacting with unfamiliar mice, both of which are good equivalents to the repetitive behaviors and social issues seen in autism.  They also looked at the pups’ brains for a protein called parvalbumin, which is a marker for a class of neurons that inhibit brain activity.  In the pups born of infected mothers, patches of neurons lacked paravalbumin.  And those pups with large patches in a part of the brain that processes touch, temperature and pain spent more time burying marbles and interacting with other mice.

When the pregnant mice were given vancomycin, which kills a certain kind of gut bacteria, the pups were normal at birth.  These bacteria stimulate the production of immune cells that produce interleukin-17A (IL17-A).  There are equivalent types of bacteria in humans.  Says the lead research on the #4 article, “Gut bacteria in maternal intestines play a critical role in shaping brain development in fetuses when mothers are exposed to inflammation.”

I remember well picking up a really bad cold in my 3rd trimester of pregnancy with Alex. And I’ve suffered IBS my entire life too, after a childhood filled with antibiotics.  I’ve always felt that my gut health (or lack thereof), led to my own autoimmune illnesses, and was tied in to Alex’s autism.  (Thus, my obsession with what grows in our gut – and thus, this blog.) Finally, I feel like there has been some major progress on the environmental cause of this autism epidemic.  Not that this is the complete answer, of course. I mean, women have always had infections during pregnancy.  The big question that remains is….what is causing this alteration in gut bacteria in moms that leads to changes in brain development in our babies?  Still, this I just a huge step in the right direction.

Now if only we knew how to treat those parvalbumin-free patches AFTER birth.

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[i] https://spectrumnews.org/news/maternal-infection-may-trigger-autism-traits-via-neuronal-patches/

More New Bacterial Microbiome Research that You Need to Know About

Two new pieces of research came out this week which I need to share.

The first I found particularly fascinating.  We know that there is a bi-directional interaction between the central nervous system and the bacterial microbiome, but HOW nerves direct bacteria was unknown.  Researchers at Kiel University, in German, using the freshwater polyp Hydra (which has a simple nervous system of only 3000 neurons) demonstrated that nerve cells release small molecules (called neuropeptides) which “…regulate the composition and colonization of specific types of beneficial bacteria…” [i] Amazingly, these neuropeptides have antibacterial activity!  As the polyp’s nervous system developed (from egg to adult), the bacterial communities covering the animal changed radically until, in adulthood, it became stable.  Not only did the neuropeptides released by the developing nervous system direct the kinds of bacteria in the biome, but also the spatial localization of the bacteria.  Near the head of the animal, there was a strong concentration of antimicrobial peptides so that 6x fewer bacteria inhabited that region than on the animals’ tentacles.

Hydra is a genus of small, fresh-water animals of the phylum Cnidaria and class Hydrozoa under the microscope for education.

Immediately, of course, I thought about “mental” illnesses like PTSD, extreme stress and anxiety, where we know that the mental trauma leads to bacterial changes in the gut.   A week ago or so, research came out showing how women with a history of PTSD have a greatly increased risk of developing lupus, for example.[ii] And lupus is associated with alterations in the bacterial microbiome.

How amazing though that the nervous system actually produces antibiotic molecules?!

A second article [iii]appeared this week which was very depressing but completely predictable.  Researchers at the University of Alberta, Canada, used a new analytical approach to look at how c-sections and formula feeding alter the infant’s developing microbiome.  They quantified the changes to gut bacteria in 166 infants throughout the first year of their lives and found that, “…compared to the normal progression of gut bacteria with infant age, formula-fed or cesarean-delivered infants showed altered trajectories of colonization among the bacterial families that have been linked to food allergies, as well as rapid weight gain.”

Says one of the researchers, “We hope this research will help clinicians and parents understand that cesarean section increases the chance of antibiotic treatment or formula-feeding of newborns, which can affect the development of gut microbiota in later infancy…”

Yeah…I know that now.  I only  wish I’d known it 23 years ago, when my son, Alex, was born.

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[i] https://www.sciencedaily.com/releases/2017/09/170926105425.htm

[ii] https://www.medpagetoday.com/rheumatology/lupus/68014

[iii]https://www.news-medical.net/news/20170926/Researchers-explore-how-C-section-formula-feeding-and-antibiotics-alter-infants-gut-microbiome.aspx

More on the Mycobiome and IBD

I just finished reading a great blog post[i] (by a post-doc scientist at the NIH) on the current state of research into the mycobiome and its effects on inflammatory bowel disease.  I learned several new things…and some things are just so important, they’re worth repeating:

  1. Those with inflammatory bowel disease have higher levels of antibodies in their blood to a yeast called Saccaromyces cerevisiae. Those with IBD also are more likely to have mutations in genes that are needed to activate an immune response to fungi.  Thus, dysbiosis of the mycobiome is common in those with IBD, including higher levels of Candida and an abnormal ratio between various fungal species.
  2. It is not yet known whether this mycobiome dysbiosis is the cause or an effect of IBD.
  3. Research in mice shows that giving S. Cerevisiae to germ-free mice exacerbates the symptoms of IBD. The yeast causes a build up of uric acid in the intestines which, in turn, over-excites the gut’s immune cells so that they start to attack the intestine itself.
  4. As I’ve written about before, there is a bi-directional relationship between the bacteria and the yeasts of the gut. Giving anti-fungals changes the amounts of different bacteria in the gut and giving antibiotics causes alterations in the mycobiome.  In fact, antibiotic use can cause such an overgrowth of yeast that it can lead to something called “fungal bloom” (a term I’d not heard before).  Apparently, a fungal bloom can potentially lead to blood poisoning (systemic candidiasis) which, even when treated, as a 50% mortality rate.

Holy cow.

  1. Perhaps most importantly of all, simply giving those with IBD antifungals does not work.  What seems to happen instead is that the medications only kill off the weakest of the fungi, leaving the resistant strains to grow unchecked.  In mouse experiments, those with IBD treated with anti-fungals actually developed worse IBD.  This fungal dysbiosis is exactly what is seen in humans with IBD.

As I read this, I thought about the vast amounts of antibiotics thrown at those with Lyme, autism, PANS/PANDAS, etc, which is especially destructive when the antibiotics are given often so early in life.  It’s no wonder, really, that recovery from these is so incredibly difficult.

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[i] https://speakingofresearch.com/tag/irritable-bowel-disease/

Helminths and Inflammatory Bowel Disease: Another Mechanism of Action

Earlier this week, I was looking through old stories in the mainstream media about using helminths therapeutically, and came across a truly excellent one (along with loads of garbage) that I had forgotten about.  It appeared in 2010, in Scientific American, and recounts the story of a man with ulcerative colitis who achieved remission using Trichuris trichuria (human whip worms).[i]  This is the single best documented case study in the medical literature.[ii]

I was particularly excited about re-discovering this one, as I was reminded of yet another astounding finding regarding helminths, apart from their direct anti-inflammatory effect and their positive effect on the bacterial microbiome.

In following the man’s case, the doctors found that as his colony of TTO died off, his symptoms flared.  During one such flare up, they found that “…immune cells in tissues with active colitis produced large quantities of an inflammatory signaling molecule named interluekin-17 (IL-17), but very little IL-22, the latter of which has been linked to wound healing and mucus production. When worms recolonized the colon, however, immune cells began manufacturing much more IL-22. Blood profiling and genetic analysis further revealed that tissues in which helminths thrived increased carbohydrate metabolism—a prerequisite for mucus production.”  (UC is associated with decreased mucus production.)

The presence of helminths causes immune cells to produce more of a molecule that leads to wound healing?!  That’s just amazing!  How it had slipped my mind, I don’t know.

Dr. P’ng Loke (one of my favorite researchers, who I have mentioned before), the lead author of the published case study, hypothesizes that “…the mucus serves as a defensive barrier between bacteria and the gut that prevents bacteria from causing inflammation and crossing over into other tissues.”

Dr. Loke was apparently stunned by his findings.  The article in Scientific American concludes with this quote, as will I: “When I first sat down to lunch with the guy who called me and he started telling me his story, I was really quite skeptical…But now I am completely changing my mind about helminthic therapy.”

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[i] https://www.scientificamerican.com/article/helminthic-therapy-mucus/

[ii] M. J. Broadhurst, J. M. Leung, V. Kashyap, J. M. McCune, U. Mahadevan, J. H. McKerrow, P. Loke, IL-22+ CD4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient Sci. Transl. Med. 2, 60ra88 (2010).

Backwards Evolution? The Case of the Increasing Allergies

I thought I’d tell you about a little noted news report[i] that seemed to receiver remarkably little attention.   According to the nonprofit organization FAIR health, severe allergic reactions to food  skyrocketed nearly 400% over the last decade.  The researchers analyzed private insurance claims in the United States involving anaphylactic food reactions. Peanuts were the most common causative agent, followed by tree nuts and seeds, eggs, crustaceans and dairy.

Peanut allergy

This, of course, only accounts for those reactions reported to insurance companies.  Can you imagine the real number then?

According to the nonprofit, Allergy UK, more than 150 million Europeans suffer from chronic allergic diseases “…and the current prediction is that by 2025 half of the entire EU population will be affected.”[ii]

Allergy UK also points out that the UK “…has some of the highest prevalence rates of allergic conditions in the world, with over 20% of the population affected by one or more allergic disorders.”

Actually, it’s scarier than that.  “A staggering 44% of British adults now suffer from at least one allergy and the number of sufferers is on the rise…In the 20 years to 2012 there was a 615% increase in the rate of hospital admissions for anaphylaxis in the UK.”

Back to that ABC News report on US food allergy rates:  their Chief Medical contributor, Dr. Jennifer Ashton says that “…it’s difficult to determine exactly why the numbers are increasing.  It appears to be the result of environmental factors, but our own immunology may be evolving and changing as well.”

Wait…what?  We’re evolving into a species that can die by coming into contact with a peanut?  That is…we’re reverse evolving?!

I wonder what Charles Darwin would have to say about that.
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[i] http://abcnews.go.com/Health/severe-food-allergy-cases-skyrocketed-past-decade-study/story?id=49345305

[ii] https://www.allergyuk.org/information-and-advice/statistics

Multiple Sclerosis: Looks Likely that it’s the Result of Altered Gut Bacteria

Trending this week in the world of the biome are two new papers[i] that  definitively show that not only does multiple sclerosis starts in the gut but also, how the gut bacteria make the immune system turn against brain nerve cells.

The first paper, out of the University of California, San Francisco, showed that two particular bacterial groups, Acinetobacter and Akkermansia, were four times more abundant in MS patients than in normal controls.  Also, another group of bacteria, Parabacteroides, was four times higher in healthy controls than in those with MS.

The researchers took naive immune cells (which turn into different types of immune cells depending on what they encounter) from those without MS and exposed them to the bacteria found in the guts of the MS patients, and these cells “…became a particular type of T helper cell, which trigger inflammation and help the immune system kill off invaders or infected cells…”  Amazingly too, Acinetobacter also “…ramped down the production of regulatory T cells, which help prevent autoimmune diseases by dampening the immune response.”

When the researchers transferred the bacteria from the MS patients into germ-free mice, they induced severe brain inflammation within 20 days.

The 2nd amazing paper was just published in the Proceedings of the National Academy of Sciences.  They looked at 34 sets of identical twins, only one of whom had MS, and found that Akkermansia was significantly more abundant in those with MS than in their healthy twins.   These researchers then transferred the gut microbes from the twins into mice and found that after 12 weeks, “…three times as many mice receiving bacteria from MS patients developed brain inflammation as those receiving microbes from healthy donors.”  And again, incredibly importantly, “Gut bacteria from MS patients also seemed to block the production of molecules, like the cytokine IL-10, that reduce inflammation.”  (IL-10 is one of the most important components of the regulatory system.)

Really amazing stuff, this.

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[i] http://www.sciencemag.org/news/2017/09/gut-microbes-could-help-trigger-multiple-sclerosis

Omega 3 Every Day Keeps the Doctor Away

Eighteen or so years ago, maybe 3 years after my son, Alex, was diagnosed with autism, I was sitting at a conference listening to a lecture on omega 3 fatty acids.  The talk really stuck with me for many reasons, especially when the speaker said, “One of the great tragedies that has ever happened in America is that mothers stopped giving their children a teaspoon of cod liver oil every morning.”

Alex was probably about 5 and my younger son, Liam, was about 2.  I bought fish oil immediately upon returning from the conference and started my boys on “fish medicine” as we used to call it.  They (and I) have taken it every day since.

Reading about new research[i] out of England made me even gladder that I’ve kept up the daily “fish medicine” tradition.  The dietary intake levels of omega 3s of 876 women were analyzed, along with their serum omega 3 levels, and the researchers found that higher levels of both was strongly associated with greater diversity of healthy species of bacteria in their guts.

It turns out that a high level of omega 3s in the blood correlates with a high level of a compound called N-carbamylglutamate (NCG) which has been shown to reduce oxidative stress in the gut.  Omega 3 seems to induce gut bacteria to produce NCG, thereby lowering levels of gut inflammation.  “We also found that specific bacteria that have been linked to lower inflammation and lower risk of obesity are increased in people who have a higher intake of omega-3 fatty acids.”

Past research has shown that omega 3s improve insulin resistance in diabetes, hypertension, arthritis, blood clots, some cancers and cognitive decline.  Seems to me that a daily dose is another one of those things you can do now that can’t hurt and could help.

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[i] https://medicalxpress.com/news/2017-09-omega-gut-healthy.html