Preventing some Polygenic Autism by Immunizing the Mother with Mycobacterium vacca bacteria - or just have Pets at Home and visit Farms.

In today’s post we look at maternal stress induced autism and how to prevent it using a bacteria from cows.  It may sound crazy, but it seems to work.

The first described strain of M. vaccae was isolated from cow dung

In the next post we will look at p-cresol autism and reversing it by a microbiota transplant. P-cresol is a chemical derived from phenol that is produced by the bacteria living in your gut. P-cresol is elevated in some young children with autism and it may explain some of those who appear to grow out of their autism.  As the level of P-cresol falls from about 7 years of age, autism symptoms fade away.

In both posts the conclusion is similar.  You are dependent on the bacteria in your environment and what the bacteria in your gut makes of you.

I did write a long time ago in this blog about the Holobiont, which is a neat idea that I think does partially explain the rise of autoimmune diseases and what is nowadays called the “autism epidemic”.

The other driver of the “autism epidemic” is the continuously evolving epigenome, where we accumulate inherited tags on our DNA, that alter expression of our genes, even though the genetic information in our DNA may be otherwise perfect.  Our genes evolve over thousands of years, but our epigenome can incorporate significant changes from each generation. An “epigenetic epidemic” is at least plausible, whereas a “genetic epidemic” is not.

Secretome,Microbiome/Hologenome, Proteome, Epigenome, Exome and Genome

In my “how to prevent future autism” advice, I do include having pets at home during pregnancy and visits to handle farmyard animals.

The reason is that over millions of years humans have evolved to depend on their environment and that includes bacteria.  The immune system is calibrated very early in life based on exposure the mother has to bacteria from numerous sources, including domesticated animals and pets.  Take away exposure to this expected-bacteria and your immune system forever lacks the knowledge it needs to protect you.  It seems to invariably over-react and we are left with people liable to allergy, dermatitis, arthritis, irritable bowel syndrome and people with polygenic disorders with an auto-immune element like autism.

In today’s post the research takes a protective bacteria from a domesticated animal and uses it to successfully immunize mothers to resist autism in their offspring. It works.

I did mention a while back that pregnant human mothers, with doggy “dust” at home, produce children who are much less prone to have asthma; doggy dust is actually doggy poo.  This may be the doggy equivalent of cows’ mycobacterium vaccae.  The Mum just breathes in the bacteria or gets it on her hands and ingests it, like Mums have been unknowingly doing for thousands of years.  Nowadays we are obsessed with buying products that kill 99.9% of germs, rather than living with them. 

Giving good bacteria to stressed mothers prevents autism-like disorder in offspring

Giving beneficial bacteria to stressed mothers during the equivalent of the third trimester of pregnancy prevents an autism-like disorder in their offspring, according to a new animal study by University of Colorado Boulder researchers.

The study, published in the journal Brain, Behavior, and Immunity, marks the latest in a series of studies in animals and humans suggesting that exposure to certain immune-modulating microbes can dampen inflammation, positively impacting the brain and central nervous system.

It's among the first studies to suggest that such exposures during pregnancy influence neurodevelopment of a fetus and, while far more research is necessary, could open the door to new prenatal interventions.

For the study, the researchers exposed rats to mild stressors and gave them terbutaline during what would be the equivalent of the third trimester of pregnancy in humans.

Half were also given a series of injections of a heat-killed preparation of a friendly bacterium known as Mycobacterium vaccae (M. vaccae), shown in previous studies to have lasting anti-inflammatory effects on the brain. A third control group of rats got no treatments.

At two and four months, the pups were given a series of tests assessing, among other things, their degree of social interaction and whether they exhibited repetitive behaviors.

As in the previous study, those whose mothers had been stressed and given terbutaline showed autism-like behaviors. But those who had been immunized with M. vaccae did not.

"Immunization with M. vaccae appears to provide some protection against the negative effects of environmental stressors during development, specifically against Autism Spectrum Disorder (ASD)-like behavior," said Smith.

Exposure to 'good bacteria' during pregnancy buffers risk of autism-like syndrome

Study in rats suggests prenatal microbial exposures influence neurodevelopment

Effects of immunization with heat-killed Mycobacterium vaccae on autism spectrum disorder-like behavior and epileptogenesis in a rat model of comorbid autism and epilepsy

Highlights

·        Immunoregulatory bacterium M. vaccae, prevents the expression of ASD-like behavior in a rat model.

·        Immunization with M. vaccae, had no significant effect on epilepsy in stress-terbutaline rats.

·        ASD-like behavior in this model does not appear to be driven by epileptiform excitability.

·        M. vaccae prevents stress-terbutaline induced microglial expression.

Abstract

Autism spectrum disorders (ASDs) and epilepsy are often comorbid. The basis for this co-occurrence remains unknown; however, inflammatory stressors during development are a shared risk factor. To explore this association, we tested the effect of repeated immunizations using a heat-killed preparation of the stress-protective immunoregulatory microbe Mycobacterium vaccae NCTC 11,659 (M. vaccae) on the behavioral and epileptogenic consequences of the combined stress-terbutaline (ST) rat model of ASD-like behavior/epilepsy. Repeated immunization of the dam with M. vaccae during pregnancy, followed by immunization of the pups after terbutaline injections, prevented the expression of ASD-like behavior but did not appear to protect against, and may have even enhanced, the spontaneous epileptogenic effects of ST. Maternal M. vaccae injections transferred an anti-inflammatory immunophenotype to offspring, and repeated injections across development prevented ST-induced increases in microglial density at early developmental time points in a region-specific manner. Despite epidemiological comorbidity between ASD/epileptic conditions and shared environmental risk factors, our results suggest that the expression of ASD-like behaviors, but perhaps not epileptogenesis, is sensitive to early anti-inflammatory intervention. These data provide support for the exploration of immunoregulatory strategies to prevent the negative neurodevelopmental behavioral effects of stressors during early critical periods.

Hopefully this new evidence will convince at least some people to take some simple steps to reduce the future prevalence for autism and other auto-immune conditions.  

Conclusion

If you buy into the holobiont/evolution theory of auto immune disease, you are left with two choices.

1.     Adjust lifestyles to be more like the old days of your great grandparents. Keep pets indoors at home and visit farmyards when planning a family.

2.     Identify the bacteria missing in modern lives and package them up like drugs

The best solution would be number (1), but I think you could make number (2) work.

Clearly avoiding stress during pregnancy is another good piece of advice; maybe easier said than done in many cases.  Having a pet should reduce stress and expose you to helpful bacteria. 

Most autism is “idiopathic”; it is polygenic meaning numerous genes are disturbed rather than in most syndromic autism (TSC, Rett etc) when a single gene is the root cause, which then causes a cascade of other genes to be miss-expressed. The origin of idiopathic autism is multifactorial, it is where you combine otherwise trivial genetic variances with environment triggers like immune over-reactions, and epigenetic tags from an ancestor who worked in a mine or even smoked cannabis.  The effects of the environment change gene expression. You have two types on genetic change, one directly from your DNA, so hard to avoid, and a second type of genetic change that was entirely preventable. Best not to pollute your epigenome until after producing children.

Cow poo is not going to reduce single gene-type autism. Cow poo might well improve auto-immune health and take away one contributing factor to the perceived epidemic of auto-immune conditions, including autism.

In reality you could add back hundreds/thousands of different missing bacteria to mimic the environment of when autism was a rare diagnosis.  Cow poo is just an example.

Secretome, Microbiome/Hologenome, Proteome, Epigenome, Exome and Genome

Biologists clearly like "–omes".

A full understanding of all the –omes would lead to an understanding of pretty much all disease, including autism.  Science is still a long way from such an understanding.

More questions than answers

Even a partial understanding of the "-omes does help to see how things fit together and also it helps understand where the research is going and why. It also makes you realize how little we currently know, and that includes all those clever scientists. This is why we keep coming back to stumbled-upon and trial error as valid discovery methods.

You can also see why researchers and those who fund them, like Mr Simons, easily get lost in the detail. Behind the 5% of the detail they fully understand is another 95% that will take a hundred years to fully understand. 

Microbiome & Hologenome/Holobiont

The intestinal microbiome is currently very fashionable.

The intestinal microbiome describes the microorganisms that reside in your intestines/gut.  It includes bacteria, fungi, viruses and archaea/protists (single cell organisms). Microbiota have been found to be crucial for immunologic, hormonal and metabolic homeostasis of their host.

The microbiome and host emerged together during evolution as a synergistic unit from epigenetic and genetic characteristics, called a holobiont.  The hologenome concept of evolution, considers a human as a community, or a holobiont - the host plus all of its symbiotic microbes. The collective genomes of the holobiont form a hologenome.

This becomes very relevant in human disease because in modern life humans have become separated from part of their evolutional holobiont (symbiotic microbes).  As a result all kinds on immune disease have become more prevalent.

It became accepted that all dirt is bad and daily contact with other living non-human animals is bad.

Humans are colonized by many microorganisms and surprisingly your body contains more  types of non-human cells than human cells. Some estimates suggest it is many times more; food for thought.

Microbiota have been found to be crucial for immunologic, hormonal and metabolic homeostasis of their host.

Bacteria are transferred from mother to child through different pathways. As the newborn’s microbiome is established, bacteria quickly populate the gut, prompting a range of immune responses and programming the immune system with long-lasting effects.

Having pets at home during and after pregnancy has been shown to have beneficial health effects on the child. Your pet dog and his bugs are part of your holobiont. If you make drastic changes in your holobiont, do not be surprised if strange things happen; a case in point are the so-called Somali Autism Clusters. When Somali refugees moved to Sweden and the US, they produced children with a high incidence of autism and all the researchers wondered why.

Secretome

This was a new "–ome" to me, that we came across in a recent post.

The secretome is the totality of secreted organic molecules and inorganic elements by biological cells, tissues, organs, and organisms.

It turned out that human fat cells secrete over 600 different different proteins/hormones.  None of this was even known 25 years ago.

So your endocrinologist knows all about the usual endocrine glands: pineal gland, thymus gland, pituitary gland, thyroid/parathyroid gland, and adrenal glands; but what about the largest endocrine gland of all, your body fat (adipose tissue)?

Genome

I did write a post about genetics, more for completeness than in the expectation that many people would read it.

The genome includes a small part of so-called “coding DNA” that contains the instructions to make proteins, this is called the exome.  The remaining 98% is made up of non-coding DNA.  This 98% used to be called junk DNA, but it is not. It is suggested that 80% of human genomic DNA has biochemical activity, not just the 2% that is the coding DNA in the exome. 

Exome

The exome is the 2% of the genome that holds the codes to make the proteins that make up your body.

Epigenome

The epigenome are all the so-called epigenetic markers that you accumulate from the environment and that you inherited from your ancestors.  You could think about this as bruises and scars on your body.  Imagine if you inherited your Grandma’s appendix scar and Grandad’s scar from a skiing accident.  In epigenetics the fact that Grandad was a heavy smoker may have marked your genes that relate to oxidative stress.

Your personal epigenome is a record of all these markers and it would show which genes are likely miss-expressed.  It would be used to determine personalized medical therapies.

This would be very relevant to autism.  

Proteome

I rather like the proteome, because it would tell you what is happening right now, rather than what might happen (as in the genome, exome and epigenome).

Most people do not realize just how much in your body is changing all the time and is not fixed at all.

The proteome is the entire set of proteins expressed by the coding DNA (the exome part of the genome), at a certain time.

So it would tell you exactly what is happening in a specific part of your body at a specific time.

This would be invaluable in understanding autism, if it could be done in real time in different parts of the brain. This is not possible with today’s technology.