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Research Shows the Microbiome Controls the Microglia: Implications for Autism?

Meg regressing2By Teresa Conrick Meg regressing3

Ongoing research is showing that the microbiome is heavily involved in Autism, a subject that very much interests me as my daughter, Megan, like many others, had severe GI issues, chronic infections, and marked regression before being diagnosed AUTISTIC.  Her regression occurred after vaccinations. Along the years, seizures developed and then an autoimmune diagnosis.  Here is how the microbiome seems to be involved:

Scientists have long wondered whether the composition of bacteria in the intestines, known as the gut microbiome, might be abnormal in people with autism and drive some of these symptoms. Now a spate of new studies supports this notion and suggests that restoring proper microbial balance could alleviate some of the disorder's behavioral symptoms….. Researchers do not yet know how exactly gut bacteria might influence behavior, but one hypothesis is that a leaky gut may allow substances to pass into the bloodstream that harm the brain.

And here are some research quotes on specific abnormalities of the microbiome and Autism:

•   Children with autism appear to have distinctly different levels of intestinal flora, which may increase their vulnerability to pathogenic bacteria and perhaps play a role in autism pathogenesis, new research suggests… "Most notably, we also discovered that the genera Prevotella, Coprococcus, and unclassified Veillonellaceae were significantly reduced in autistic children”  

•   Fecal flora of children with regressive autism was compared with that of control children, and clostridial counts were higher. The number of clostridial species found in the stools of children with autism was greater than in the stools of control children. Children with autism had 9 species of Clostridium not found in controls,  

•   We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder. 

•   Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites. 

Let’s look at the immune system and Autism, which hasbeen an increasingly hot topic for well over 10 years but we don't hear about it enough in the media:

The Immune Response in Autism: a new frontier in autism research,  May 12, 2006  

…increasing research has focused on the connections between the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early in embryogenesis and persist throughout an individual's lifetime, and successful neurodevelopment is contingent on a normal, balanced immune response....There is emerging evidence and growing concern that a dysregulated or abnormal immune response may be involved in some forms of ASD...Various hypotheses have attempted to link dysfunctional immune activity and autism, such as maternal immune abnormalities during early pregnancy, increased incidence of familial autoimmunity, and childhood vaccinations.

The connections are becoming more apparent now:

The Microbiome and Neuroimmunology, Sept 1, 2015 

Many studies are showing that an individual’s microbiome influences gastrointestinal health. The impact, however, of commensal microbes on most other body systems is still emerging. Recently, there have been several discoveries linking the microbiome and the nervous system.

In a paper recently by Erny et al. investigated modulation of microglia by the microbiome. Microglia are the immune cells of the central nervous system, protecting the brain and maintaining healthy neural circuitry. People with microglial deficiencies are susceptible to neurological and neuropsychiatric diseases..…This paper is interesting as it describes a previously unknown interaction of the human microbiome with both the immune and nervous systems.

Here’s a portion of the abstract from that study:

Host microbiota constantly control maturation and function of microglia in the CNS.  Epub 2015 June

As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features….These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.

What that means is that the Microbiome is vitally connected and constantly controls the immune cells of the Central Nervous System, the microglia.  What makes that so interesting and very pertinent for my daughter and many more, is that the microglia are very much implicated in the genesis of Autism:

Evidence indicates that children with autism spectrum disorder (ASD) suffer from an ongoing neuroinflammatory process in different regions of the brain involving microglial activation. When microglia remain activated for an extended period, the production of mediators is sustained longer than usual and this increase in mediators contributes to loss of synaptic connections and neuronal cell death. Microglial activation can then result in a loss of connections or underconnectivity. Underconnectivity is reported in many studies in autism. One way to control neuroinflammation is to reduce or inhibit microglial activation. It is plausible that by reducing brain inflammation and microglial activation, the neurodestructive effects of chronic inflammation could be reduced and allow for improved developmental outcomes.

This shows how interventions like diet, probiotics, and fecal microbiota transplants would be helpful, as the former researchers reported – “microglia impairment can be rectified to some extent by complex microbiota.”  Or as quoted here,   —“Researchers also demonstrated that recolonizing microbiota populations in mice was able to restore microglial integrity. “

This is good news as it strengthens the microbiome connection to Autism and illustrates HOW the gut and brain are in an intimate relationship. More analysis:

To Be Hale and Hearty, Brain Microglia Need a Healthy Gut, 05 Jun 2015  

 The human intestine contains a rich mosaic of microbial cells—around 1,000 different species—that help digest food, block pathogens, and maintain general good health. A paper in the June 1 Nature Neuroscience assigns the gut microbiome yet another role. Researchers led by Marco Prinz, University of Freiburg, Germany, found that these microorganisms help mature and bolster the brain’s resident macrophages, known as microglia. The connection appears to hinge on short-chain fatty acids produced by the bacteria as they digest food. While there are no obvious implications yet for neurodegeneration, microglia are increasingly recognized as important players in diseases such as Alzheimer’s and Parkinson’s. Grasping the cells’ basic biology could offer clues to these disorders.

“Understanding more about what regulates the maturation, growth, and responses of microglia within the CNS is a critically important area,” said Terrence Town, University of Southern California, Los Angeles, who was not involved in the study. “This study illustrates the dynamic and complex interplay between gut flora and microglia—not an obvious connection.”.....Scientists already knew that gut flora influenced a variety of peripheral immune cells. Mice raised without microbiota—known as germ-free—have immature and underperforming immune systems (for a review, see Round and Mazmanian, 2009). However, no one had explored whether microorganisms in the intestine help mature and maintain the brain’s immune cells, which are locked securely away behind the blood-brain barrier.

It wasn’t just the cells’ maturation and appearance that took a hit. Their reaction to infection also faltered.

Strange that Autism is not mentioned in any of this, though the mention of Alzheimer’s and Parkinson’s is a good hint of connections.  That last sentence – “Their reaction to infection also faltered” –  would describe much of the Autism that Megan has and many others. The photos of her above show how devastating the regression was as she developed infection after infection then lost both receptive and expressive language, lost eye contact, and became timid of everything, especially sounds.   Autism for her was an existence of illness, pain and no communication.  Knowing that the microbiome is a key to altering the brain is significant and very hopeful.

Teresa Conrick is Contributing Editor to Age of Autism.

Comments

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Benedetta

Thank you for the link.
My Dad has Parkinson.

Those who consume more carbohydrates, especially fibre, the Prevotella species dominate.

He could live off of pies and cakes and did; main thing for him and his diet is corn bread. I have cut back the sugar and all of the gluten. He still is getting worse. I just want to halt it.

Greyone

This article mentions the prevotella also, in relation to Parkinsons.
http://bobcowart.blogspot.com/2015/10/bacteria-levels-in-gut-relate-to.html

Benedetta

VP:

Thank you for the link. IT was a very interesting article. Here is study I found interesting too - relating to microbiome and interleukin.

http://www.nature.com/nm/journal/v20/n11/full/nm.3680.html

Regulatory B cells are induced by gut microbiota–driven interleukin-1β and interleukin-6 production

VP

The connection to autism is interleukin-6, explained in this series of articles:

http://vaccinepapers.org/immune-activation/

Angus Files

Thanks Teresa plenty to chew over as always, great work.

MMR RIP

susan

Surely this was what the research by Dr. Wakefield, Prof Walker Smith et al found? (Or am I missing something?). If so, further research for the last 15+ years could have saved so many families from trauma.

Teresa Conrick

Hi and thanks! Lisa, wanted to say yes-- to the interventions that you have mentioned -- they each have and continue to be successful for us. FMT will be happening more. The research on schizophrenia is including more on the microbiome as well-

http://www.nature.com/mp/journal/v19/n12/full/mp201493a.html
Genomics of schizophrenia: time to consider the gut microbiome?


http://www.sciencedaily.com/releases/2015/08/150825083616.htm
Microbiomes of human throat may be linked to schizophrenia
Studying microbiomes in throat may help identify causes and treatments of brain disorder
Date:
August 25, 2015
Source:
George Washington University
Summary:
In the most comprehensive study to date, researchers have identified a potential link between microbes (viruses, bacteria and fungi) in the throat and schizophrenia. This link may offer a way to identify causes and develop treatments of the disease and lead to new diagnostic tests.

http://www.ncbi.nlm.nih.gov/pubmed/25034760
Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

Carol

How does geography affect microbiome? I would expect the microbiome of a kid in China to be different in certain respects.

Denise Anderstrom Douglass

Thank you, Teresa. The research is growing and it is starting to fit the picture we know: repeated infections, antibiotics, tylenol, eating problems, boom-- rapid regression after vaccines, including MMR, horrible bowel issues, and on and on. Thank you!

Benedetta

Thank You Mary for the link -- A protocol of probiotics on an empty stomach twice a day, NSAIDS taken with food, antivirala drugs, anti fungi drugs. And as always diet I did not see what the diet was but I assume low glycemic - low carb- wheat free- dairy free -peanut free.

Than you Teresa for this article- taking the time to read all these studies and get the together for us, and summarize them for us.

We have more of two types of microbes so far - and less of several others.

Microbes affect the immune system of the body and the brain. They still have not turned it around to see if the brain can effect what grows in the GI track though?

B vitamins and all that implies with nerve health and chicken and egg.

On the home front - lacto fermenting but too much makes us sick. But I have found that when I make cole slaw the regular way - I can put in a cup of sauerkraut and that is working for us.

Another thing I found that I wonder if it has been going on for 1000s of years - is lacto ferment something on a rainy day and in the dryer fall - dehydrated the fermented stuff.

I love dehydrated lacto fermented peppers - wonderful - and dehydrated sauerkraut is really good. It gives salads a crunch since croutons have long since been out of our diet.

Lacto fermenting and then dehydrating gives more B vitamins and some microbes will live - just not so many.

Example of how life is stubborn - I separated blackberry juice from seeds two years ago. I thought the seeds would make good fertilizer if I killed them. I steamed them really good before putting them on my lettuce beds. There was something in the blackberry seeds that would not let the lettuce seeds sprout - and I had a lot of the blackberry seeds still able to sprout I pulled them all up and have had two good lettuce beds since. This fall -- a little blackberry plant tried to come up -
And so I would assume thus goes the way of the microbes in fermented food when you dehydrate it.

I notice that some of these microbes are just recently discovered.

I look so forward to more of your post Teresa Who would have guess that microbes were important in damping the immune system. I mean not to make us weak - but to make us strong!


Gary Ogden

Fascinating. The relationship of the microbiome to health and its role in a host of modern ills is becoming clearer by the day. I find this enormously interesting. This is where our research dollars should be going. The structures of the gut-brain axis have been recently identified. Gut dysbiosis is clearly linked to autism in many, and treating that should help many. A healthy gut is crucial to good health for everyone. Thank you so much for this, Teresa.

Maurine Meleck

Thanks Teresa. I learn so much from you early in the morning.

Lisa

Thank you, Teresa, once again for your excellent work. I am following this line of research very closely now myself. I have a brother with schizophrenia, so it is very relevant for us.

Since my mother's death last year, I have begun spending a lot more time with my brother. I am starting to notice patterns in his illness that strongly hint at the possibility his form of schizophrenia is actually autoimmune. When he has what I will call a "flare-up," it starts with extreme fatigue that lasts for several days to a week or longer. This is followed by several weeks of "blank mind" where he sits and stares into space, almost catatonic, for most of the day. He loses all interest in everything, including his two little dogs. Gradually he comes out of it, but he never completely recovers.

I have been thinking a lot lately about why he never has a full recovery in between these flare-ups. Part of it, for sure, is the drugs he is given, none of which treat his underlying immune dysregulation, and all of which make it very difficult for even a healthy person to function normally. But I'm also starting to hone in more on the microbiome, and thinking maybe the reason he doesn't ever fully recover is because the microbiome itself never fully recovers between these bouts. So I'm starting to think that, aside from getting off all of the horrible drugs he's been prescribed by psychiatrists for years, figuring out how to heal his gut is the key.

To that end, Teresa, I'm wondering which therapies you've tried for Megan -- specifically, have you tried Minocycline, Diflucan, other anti-fungals, probiotics? I'm curious to know which treatments people are finding most efficacious. Also, I'm very interested in the fecal transplant research but haven't seen much yet in terms of its efficacy with autism and/or schizophrenia.

mary w maxwell

Bewdy! Teresa, have you heard of Juan Rodriguez microglial protocol? He says this re his son:

"A few years ago Daniel didn't even know how to play with anything, even less even throw a ball or swing a bat. Now Daniel is being off all medications and diets for over 2 years now and didn't regress. Daniel has also graduated from all the ABA, speech, food and OT therapies that he took in the past.
Juan Rodriguez is sharing hope, knowledge, a new way of thinking about how medicine should be practiced and how the epidemic of autism can be ended." (at stopcallingitautism.org)

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