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 

Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels 

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:

Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

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.