•   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.