Brain on Fire the Microbiome Autism and Autoimmune Encephalopathy Part 2
In Part 1 , we took a look at autoimmune encephalopathy and the emerging research in autism. Much of it had a focus on autoantibodies. Now, I’d like to investigate the microbiome and its connection to both autism and autoimmune encephalopathy. Again, follow the studies as they are showing patterns that are important for autism:
This paper discusses Multiple Sclerosis and Rheumatoid Arthritis yet its value in autism research cannot be denied.
The gut–brain connection: triggering of brain autoimmune disease by commensal gut bacteria, 2016
However, the discovery that intestinal microbiota are able to trigger autoimmune disease in organs far away from the gut, in the CNS, was less anticipated. How could gut microbes ignite an autoimmune attack against the CNS, an organ not only far from the gut, but also enveloped by seemingly tight tissue barriers? First, it should be remembered that tissue-specific autoimmune diseases are driven by autoimmune T cells with receptors specific for tissue-specific autoantigens. Second, such self-specific T cells are normal components of all immune systems, healthy as well as diseased. They sit in the immune system in a resting mode, innocuous. Only upon particular stimuli that trigger their activation, do the self-specific T cells unleash their autoaggressive pathogenic potential…….
….antibiotic treatment not only altered the gut microbiota, but also mitigated clinical CNS inflammation. They attributed the effect to a decrease of Th17 cells in the gut, possibly effected by invariant T cell populations [31]. Subsequently, Kasper and colleagues discovered in a similar model that the expansion of a particular bacterial species, Bacteroides fragilis, reduced autoimmunity. The microbes seem to release a capsular polysaccharide A for recruiting and activating intestinal regulatory T cells in the colon [32]. Lactic acid bacteria were also reported to protect against EAE responses, though by activating another regulatory T cell population, IL-10–producing Tr1 cells [33].
At that time, the investigators considered pathogenic microbes to be triggers of the autoimmune disease [35]. But it has turned out, recently, that the potential to set off spontaneous EAE is not necessarily restricted to pathogenic bacteria, but is also a property of non-pathogenic commensal microbes.
Autoimmune diseases do not develop at random; they arise in individuals with a propitious genetic profile, and they must be triggered by special environmental stimuli. Intriguingly, as it has turned out recently, the site of stimulation may not be within the target organ itself, but remote, in the bowel. The mechanisms that drive the remote seem to involve a pro-inflammatory interaction between the commensal gut flora and autoreactive T cells with receptors for brain autoantigens.
SO it is both the good and bad bacteria that can cause the brain autoantigens. That is important also in autism.
Let’s look at a study that again, is not about autism, but it actually may need to be examined for a connection:
Cross-Immunoreactivity between Bacterial Aquaporin-Z and Human Aquaporin-4: Potential Relevance to Neuromyelitis Optica, 2012
NMO is an autoimmune disorder of the CNS that is mediated, in part, by a self-reactive Ab against astrocyte Aqp4 protein. The goal of this study was to examine whether an autoimmune response against Aqp4 may arise through a mechanism of infection-induced cross-immunoreactivity….
Based on these results, we concluded that bacterial AqpZ and human Aqp4 proteins share significant structural homology and cross-react in immune-based assays and experimental systems. Thus, our study provides direct evidence that infection-induced cross-reactivity may be involved in the induction of the autoimmune response against Aqp4 in NMO. The findings of our study are novel and provide a new perspective on the pathogenesis of NMO. Our study indicates involvement of a bacterial pathogen in NMO. Microbial trigger has also been considered in several reports, based upon circumstantial associations of certain infections with the disease onset (e.g., Mycobacterium tuberculosis and Helicobacter pylori) (6, 43–45). In addition, Th17 cells mediating host defense against extracellular bacteria are involved in NMO.....Overall, this hypothesis is in line with the pathogenic patterns of some of the paradigmal autoimmune diseases of the nervous system, such as Sydenham’s chorea and Guillain-Barre ´syndrome (30, 31).
Here we see again, infection can lead to autoimmunity. Now, check out what they found out four years later:
Gut Bacteria Linked to Rare Autoimmune Disease Overabundance of Common Species in ‘Microbiome’ May Cause Inflammation, 2016
A new study led by UC San Francisco scientists shows that a bacterium commonly found in the human gut is overrepresented in patients with a rare, often disabling autoimmune disease known as neuromyelitis optica, or NMO. The researchers suggest that the greater population of this bacterium, Clostridium , that they observed in NMO patients may play a role in development of the disorder....
In NMO, which until quite recently was thought to be an unusual form of multiple sclerosis (MS), the immune system attacks neural support cells called astrocytes. Specifically, NMO targets one type of the astrocytes’ water channels, structures also known as aquaporins, which allow water to rapidly flow in and out of cells. Repeated immune assaults on these channels in the spinal cord and optic nerve create lesions that can lead to paralysis or blindness. Unlike MS, there are no approved therapies for NMO.
“We don’t know what causes NMO, but we wondered if some organism could be fooling the immune system into attacking itself,” ... the work provides support for a theory of “collateral damage” that he and others are actively exploring: a certain amino acid sequence of a C. perfringens protein matches a sequence in the aquaporin targets in NMO, which may prompt the immune system to launch an attack on the bacterium that also incidentally targets the water channels.
It’s the bacteria CLOSTRIDIUM perfringens that is “fooling the immune system into attacking itself.”
Is that relevant in AUTISM? Yes:
Toxin profile of fecal Clostridium perfringens strains isolated from children with autism spectrum disorders.
Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children
What could this bacteria be doing to cause autism symptoms? Let’s look at more evidence….
The gut microbiota and the emergence of autoimmunity: relevance to major psychiatric disorders
The search for autoantibodies reactive against brain proteins is an ongoing quest that has been enthusiastically pursued and simultaneously disputed for a long time [ 12, 15, 22, 78–86] [87–90]. The glutamate NMDA receptor serves as a currently well-discussed antigenic target in this context [8, 12, 91–96]. Other sources of autoantibody activity relevant to psychiatric disorders include Neuregulin-2, HERVs, cholinergic muscarinic receptors, nicotinic acetylcholine receptors, dopamine D2 receptors, mu-opioid receptors, serotonin receptors, AMPA receptors, GABA receptors, GAD, potassium channel receptors, cardiolipin, DNA, histones, mitochondria, [12,93-95]..... The diversity of antigens that may precipitate the production of autoantibodies extends to microbes and the discussion of another relevant disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). In PANDAS, certain behaviors such as obsessive compulsive disorder and tic disorders are attributable to brain-active autoantibodies generated in response to a streptococcal infection [97-98]....
PANDAS and PANS. More and more of our kids are evolving from or into those two entities--both with an autism diagnosis or without. I appreciate this study as it too, takes a look at what is going on in the gut microbiome of identified PANDAS/PANS patients:
The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. ...In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.
We appreciate and need MORE research and MORE treatment options. This text message from a friend, a fellow warrior watching her son for years now become more sick, DIAGNOSIS: Autism and PANS -
“He spent 15 HOURS (from 6pm last evening until 9 a.m. this morning) in nonstop OCD mode where he “knees” all over the floor - basically he uses his knees as feet and “walks” all around on his knees. The other day he spent 12 HOURS trying to leave the bathroom after using the toilet - he just gets stuck in these never ending ocd loops. It’s the worst and just keeps getting worse! “
Heartbreaking.
Teresa Conrick is Science Editor for Age of Autism.
@Michael - thanks for your support. I think the big challenge of homeopathy is finding the right remedy for an illness or affliction, and for something as complex as autism, that's an even bigger challenge.
@Grace - thanks too for your thoughts. I always do appreciate your perspective. I thought it was interesting what you said about how many Aspies don't seem to fully grow up. Of course, that might be said for many neurotypicals too! I'm sorry you didn't get the kindness and support you needed throughout your life. I, at least, wish you the very best, and I enjoy our interchanges here on AoA.
Posted by: Aimee Doyle | September 08, 2018 at 09:13 AM
@Aimee, I was fortunate that the homeopath I stumbled on (probably with some divine intervention) and her training found the right remedy (the third one). I remember asking the homeopath, "what if this doesn't work" and the response was find a different homeopath. I will query my homeopath with what you have provided and just see what comes back.
I also see the foundation cracking--I can almost hear it faint as it is.
Keep the faith!!
Posted by: michael | September 07, 2018 at 01:29 PM
Aimee,
Thank you for your long description of your son's difficulties. I didn't mean to make light of them. I actually find it helps me to hear about the ways autism affects those who have a severe case, as I get no support with mine, and I've had to work it out for myself. I can see how difficult this must be to deal with, and you've obviously tried all that there is out there. I don't know if it helps at all, but other Aspic people I know appear in some ways never to grow up. I feel a bit that way myself at 65! I suppose those of us who are able to have jobs have something to "lose ourselves" in. Also, sometimes when something we fear actually happens, it turns out not to be so bad. Maybe that would apply to your son, I don't know, but also how to get him to see that. I can only wish you progress with it in the future.
Posted by: Grace Green | September 07, 2018 at 09:00 AM
@Michael - thank you so much for responding. Thank you for caring. And I agree with you about the church of immaculate vaccination. Not sure what it would take to shake that faith, although I do think there are some cracks in the foundation.
We actually did try homeopathy with our son, on two separate occasions. We worked with a naturopath for a couple of years after he was diagnosed, and she tried a number of homeopathic and herbal remedies. While I liked her a lot, I don't think her treatment was particularly helpful.
Then, when he was an adolescent, we worked with a classical homeopath (a Heilkunst practitioner) for a number of years. I do think it was helpful because his behaviors improved a lot - no more out of control screaming, no more walking on the knees. But it ultimately was not the silver bullet. Her theory was that his autism was karmic and likely could not be healed at this level. Not sure I buy that, but when you deal with alternative health providers, you encounter some out-of-the-mainstream beliefs. The theory of Five Levels of Healing, however, was very interesting to me. (Work of Dietrich Klinghardt).
We've tried every treatment in autism (and have the debt to prove it) - from the conventional (ABA, pharmaceuticals), to the alternative (supplements, GFCF diet, secretin, methyl B-12 injections, homeopathy, acupuncture, craniosacral), to the downright fringe (energy work). Most things have helped to some extent, but his anxiety, though not as severe as in adolescence, is still fairly crippling.
If you have someone good to recommend, though, in terms of homeopathy or another modality, I'll be happy to check it out. I'm pretty open minded.
Posted by: Aimee Doyle | September 06, 2018 at 08:20 PM
Aimee,
Justice Breyer concurring in Brusewitz https://www.supremecourt.gov/opinions/10pdf/09-152.pdf page 26 references "Impact of Anti-Vaccine Movement on Pertussis Control". It is clear that the majority opinion that parents should be willing to sacrifice their children to this religion of vaccinations that was sanctified in Bruesewitz and furthermore all forms of due process should be forever denied to protect the religion.
"Walking on knees" made me curious so I looked in my Kent's Repertory of the Homeopathic Materia Medica under MIND;Delusions; walk--that he walks on his knees. I am not suggesting a remedy here, but it did get my attention. I didn't have time to look under mind "stay young" but I am thinking that a very good homeopath might be able to work with the symptoms you have provided. Was there an opportunity to try homeopathy with your son?
Posted by: michael | September 06, 2018 at 01:23 PM
@Grace - I agree that a fear of independence is not a disorder. But my son's fear and anxiety on this issue really are extreme.
My son can't actually have a conversation about this. Although he has some language, he doesn't have the ability to converse back and forth, particularly on an issue that creates so much anxiety for him. If you ask him why he has fears, he says he doesn't know. He doesn't want to talk about his fears. If we persist, he goes into Disney script and gets angry. And it's more than a fear of independence - it's a fear of growing up.
Let me give some examples of why I think this is so limiting. He will not cut up his meat or waffles or pour his own juice, because "little boys don't do that." He will not dry his own hair. He will not shave himself. If I try to tell him "little boys do that" then he simply repeats what is said. He refuses to celebrate his birthday because he does not want to admit he is getting older. He does not want to move out or get a job... and guess how that impacts all the person-centered planning that adult services want to implement.
He hates the "J word" (Job) and the "G" word (graduate) and becomes furious if anyone uses them. Just saying the word "teenager" would drive him into a rage in adolescence, and he still can't tolerate anyone saying the word, or any of the numbers between 12 and 20 (they all end in "teen"). We can't say any year that ends in a "bad number", like 2018. We can't say any year that started with 19, e.g. 1990. Using the wrong words is one of the few things that will cause him to get aggressive to others. For a number of years (and it still crops up occasionally), he would talk about how he wanted to run out into the street, get "run over flat", and reincarnate and be a little boy again. (Not sure where he got the reincarnation idea). That was very frightening to us, and there are times I think he might have done it, barring our locked doors.
I would LOVE a solution to this. I do appreciate your advice, and I wish it would work. But my husband and I have honestly tried to talk with him on these issues, and he simply refuses. Others have tried to talk with him about this (doctors, family members, teachers, and even one or two adults with autism that we know). I guess fears don't usually respond to logic. We have tried a number of other solutions to decrease his anxiety, without much luck.
Posted by: Aimee Doyle | September 06, 2018 at 12:15 PM
@Sophie Scholl...my child actually has Autism Related Catatonia and does the EXACT same things as you describe. Those and dozens of others issues. Getting stuck everywhere. Please research Autism Related Catatonia and get him help. Most doctors do not have a clue about the diagnosis and it gets missed ALL the time. Delaying getting your child help only makes it worse. There are very few doctors in this country who understand Autism Related Cat. but there are a few out there. The diagnosis is a nightmare for the person and for those caring for the person.
Posted by: a parent | September 06, 2018 at 10:14 AM
Aimee,
Fear of being independent is not, IMO, a disorder. Please, think it through, and then sit down with your son and have a long and rational conversation. I've been thinking a lot about this as a result of accusations that I'm depressed, when I'm not, and realizing that they now call anxiety depression, and I have good REASON to be anxious! Firstly, no-one is an island, we are all interdependent. People are dependent on society, public services, infrastructure, and other individuals. The autistic person knows people don't understand him, or like him, and that he may have little to offer to society in return. He is alone and knows it. I'm sorry if this is worrying for you, but it's better that you try to find solutions, and be open about it with your son. In my experience, autistic people get on better with family members, and preferably in small numbers at a time (perhaps on a rota). Alternatively, there are some communities which might be suitable in the longer term. I do believe that if you discuss this with your son he will be able to understand his fears and will be better able to deal with them.
I hope this is helpful to you and any other families facing these symptoms.
Posted by: Grace Green | September 06, 2018 at 07:09 AM
Sophie: Have you researched "Autism-related Catatonia"? As part of that condition, my son has difficulty making simple decisions or going thru doorways sometimes. Best wishes.
Posted by: Andrea | September 05, 2018 at 10:27 PM
I am sorry Aimee. Anxiety is a major problem for us too.
Yet, my son tries so to be brave, even when I know he is scared. He is 32 and doing his best to be manly.
Posted by: Benedetta | September 05, 2018 at 10:15 PM
@go Trump
J. Kavanaugh's judicial record does not reflect a man who is protective of the rights of individuals with disabilities. A significant number of major organizations that fight for disability rights are opposed to J. Kavanaugh. I can give you a list if you'd like. Also, I'm an attorney, and the mother of an autistic son (who will need lifelong care and support) and I've read some of his decisions. I can understand why there is outrage on the part of the protesters. I haven't seen a decision where J. Kavanaugh is friendly to the rights of the disabled.
But regarding outrage, why aren't you upset about our Republican president, our Republican controlled Congress, our Republican controlled Government Oversight and Reform Committee, our Republican heads of HHS, FDA, and CDC, or our Republican controlled Supreme Court? These are the people in power, and I can't see that they are doing anything about vaccines or autism. Why are you giving them a pass? What are they doing that is "productive"? Maybe tomorrow...glad all the vax-injured kids can wait.
BTW, read J. Gorsuch's opinion from 2008, when he was a judge on the 10th Circuit Court of Appeals, against an autistic child and his parents. Endrew F. v. Douglas County School District. Or check out J. Scalia's majority opinion in Bruesewitz v. Wyeth. No friend to autism or vaccine safety advocates there. Do we really need another anti-disability rights voice on the Supreme Court?
We do need to address the vaccine issue. I agree that it's critical. But I don't see either side of the aisle doing that. But I think it's important we remember that once kids are disabled, they need IDEA, SSI, Medicaid, etc. and lots of support ($$$) for things like housing and employment. The recovery rate from autism is under 10%. Fixing the vaccine problem - even if it happened tomorrow (which doesn't seem likely) will still leave hundreds of thousands of children and adults who need lifelong care, and yes, government support, since most families can't handle the devastating costs of lifelong disability. I worry about my son's safety net being ripped out from under him.
Posted by: Aimee Doyle | September 05, 2018 at 08:55 PM
Off topic, but interesting watching the Kavanaugh SCOTUS hearings.
Lots of paid ? protesters that shout out once in a while... I wish they would behave, but perhaps they might say “Ban Vaccine Mandates” or “Vaccines cause Autism” if they need something productive to say ... perhaps tomorrow.
Posted by: go Trump | September 05, 2018 at 07:06 PM
I have also experienced this type of all pervasive, bone deep anxiety that does not center around an object or concrete experience but a concept.
I have been curious-have any of you heard of vaccine induced autism that occurred several months after the vaccine. I developed symptoms of autism gradually, not overnight, after DTP. People I’ve spoken to have said even if vaccine induced autism exists, the damage would have to occur immediately.
Posted by: JT | September 05, 2018 at 05:23 PM
Regarding the text message from a fellow warrior mom/dad...
I feel for you. My autistic son has an anxiety disorder overlaying his autistic disorder. Not exactly OCD, but similarly difficult. Your comments about walking on knees brought back some intense memories.
The anxiety disorder in my son manifests as a profound fear of growing up and being independent. As an adolescent, he hated the fact his body was growing, so he would walk on his knees to "stay young." He did this whenever he could and just about wrecked his knees due to inflamed bursae. He also hit his legs over and over again, trying to make them go back to being "young." He hated the fact that his legs had grown hair. For a couple of years he had semi-permanent bruises on his thighs.
He's 28 now and has calmed down somewhat in that he no longer hits himself or walks on his knees. He still fears growing up however, and as a result, does not want to be independent, or to develop any skills that might make him independent. When someone asks him what he wants, he says "I just want to stay young."
We have tried many things to try to calm his fears ( various biomedical interventions, supplements, medication, behavioral modification, acupuncture) without much success.
Posted by: Aimee Doyle | September 05, 2018 at 03:46 PM
Theresa … god bless you for your tireless effort "investigating the microbiome and its connection to both autism and autoimmune encephalopathy". You do the "journalistic investigative" work that others in that profession absolutely refuse to do. Unfortunately .. there are those courageous few in the medical and psychiatric professions that do seek to identify the connection .. and … just as Dr Wakefield before them .. are severely criticized for doing so.
I am … AGAIN …. recommending our AoA community take about an hour and view an ABC 20/20 episode broadcast in July .. about PANDAS .. Pediatric Autoimmune Neuro Psychiatric Disorder Associated with Streptococcal infection.
https://abc.go.com/shows/2020/episode-guide/2018-07/20-072018-pandas
It was positively frightening to see desperate parents trying to explain what happened to their perfectly healthy children .. OVER NIGHT .. which one dad describes as saying … "Someone entered our child's room at night while they slept and took our child .. leaving behind a child that is completely different .. indeed dangerous … to themselves and our entire family".
The personal and professional attacks on those few courageous physicians who believe the OVER NIGHT change in a child's BEHAVIOR is due to contracting Strep .. which somehow crosses the brain barrier causing BIZARRE neurological behavior changes.
Predictably … the PARENTS are told THEY are responsible for their child's OVER NIGHT BEHAVIOR CHANGES .. the two most popular accusations .. GENETICS AND ABUSIVE CHILD EXPERIENCES (ACE'S). The common recommendation .. in almost every instance .. is for parents is to voluntarily COMMIT their child to a psychiatric facility .. where the child will be prescribed MOOD ALTERING DRUGS as the remedy.
It really is a program worth watching … I highly recommend it to all.
Posted by: bob moffit | September 05, 2018 at 02:45 PM
My hope there is a Part 3 where the doors are burst open and those incarcerated are set free. Thanks Teresa!
Posted by: michael | September 05, 2018 at 12:55 PM
Do you think that is why the studies are showing that the TB vaccine - after two or three years on down the line helps those with MS and diabetes because it is encouraging the immune system to finally go after Clostridium perfringens, or the Mycobacterium tuberculosis or even Helicobacter pylori?
The NIH meeting on the microbiome said vaccines were like a sledge hammer; killing out good as well as the bad and making room for who knows what. We kill all types of microbes that even resemble the targeted microbe by forcing our own immune systems with a vaccine to do so. We are leaving an empty niche to be filled, and it is being filled with yet another type of tetanus - clostridium.
The recent talk about using a TB vaccine helping as with any vaccine; causes initially inflammation that is a good chance to kill you dead or disable you and then later - yeah later, empty niches to be filled with - what? Things that makes us anxious? OCD? Depressed? Or maybe we will do better?
Talk about a shot in the Dark! Wow that book title is taking on even more meaning, as the years roll by.
Posted by: Benedetta | September 05, 2018 at 11:37 AM
Is anxiety another, milder form of OCD?
Posted by: Benedetta | September 05, 2018 at 11:15 AM
Thanks, Teresa. This is fascinating work. Absolutely applicable to autism. I wonder what, if anything, is being done in altering the gut microbiome to reduce symptoms of these autoimmune conditions. It doesn't make sense that the body would attack itself, not in a chronic way. Medicine isn't interested in solving such things, but surely Science is.
Posted by: Gary Ogden | September 05, 2018 at 09:39 AM
“He spent 15 HOURS (from 6pm last evening until 9 a.m. this morning) in nonstop OCD mode where he “knees” all over the floor - basically he uses his knees as feet and “walks” all around on his knees. The other day he spent 12 HOURS trying to leave the bathroom after using the toilet - he just gets stuck in these never ending ocd loops. It’s the worst and just keeps getting worse! “
Get it right - crime against humanity is what it is (deliberate too)
Posted by: Sophie Scholl | September 05, 2018 at 07:43 AM