Autism and the gut-brain axis

While the acceptance of autism has increased considerably in recent decades, we still know very little about the underlying causes of this disorder.

One of the biggest puzzles with regard to autism is the phenomenon that a very large number of people with an autism spectrum disorder also have intestinal complaints. So there is definitely a relationship between the gut and the brain.

It seems however that the root cause of this relationship has finally been clarified by showing there's a link between inflammation (more specifically IL-17a), gut health and autism. 

How inflammation and gut bacteria influence autism

In the research discussed below, the relationship between autism, the immune system, gastrointestinal issues, and gut bacteria was studied.

Characterized by difficulties with socializing, and often accompanied by repetitive behaviors, this neurodevelopmental disorder harbors many mysteries.

Despite its prevalence and a glut of research, the causes behind Autism spectrum disorders (ASD) are still not fully understood.

Although ASD primarily impacts the brain, over recent years, links with other systems have become clear — in particular, gastrointestinal (GI) issues seem to occur more often in individuals with ASD than in the rest of the population.

In one study, compared with typically developing (TD) children, those with ASD were six to eight times more likely to report GI symptoms such as bloating, constipation, and diarrhea.

Other studies have shown that children with ASD who experience GI problems are more likely to have more severe symptoms of ASD. Also, treating the GI symptoms can sometimes relieve the behavioral and social symptoms of ASD.

Interestingly, behavioral issues are found alongside other conditions that impact the gut. For instance, people with celiac disease are more likely to have autism-like traits and other psychological symptoms. The gut and behavior seem tied together in some way.

According to many researchers, the GI issues that come with ASD might be due to two factors: firstly, inappropriate immune activation, causing inflammation of the tract; and, secondly, differences in the types of gut bacteria that are present.

However, the picture is still incredibly murky, and studies produce differing results, finding different types of inflammation and various changes in gut bacteria.

The gut and the immune system

Recently, researchers set out to investigate these relationships in more detail.

The scientists examined 103 children, aged 3–12. The participants were split into four groups:

• children with ASD and GI problems (ASD+GI)
• children with ASD but without GI problems (ASD)
• TD children with GI problems (TD+GI)
• TD children without GI problems (TD)

To assess both the immune response and gut bacteria, the researchers analyzed blood and stool samples.

Children in the ASD+GI group showed a number of differences compared with the other three groups. For instance, they had higher levels of inflammatory cytokines — which are signaling molecules that promote inflammation — such as interleukin 5 (IL-5), IL-15, and IL-17.

Both the ASD+GI and ASD children had lower levels of TGF beta 1, a protein that helps regulate the immune system and keep it in check. The fact that this change was measured in both groups is an interesting finding; it suggests that children with ASD but no GI symptoms could be experiencing other inflammatory conditions.

“It’s significant that the regulatory aspect of the immune system is decreased, which puts them at risk for inflammation. ”
“Many studies point to different types of inflammation, and I think this one kind of summarizes why all those other findings can be true at the same time.”

TGF beta 1 is also known to be important in neurodevelopment, so this protein could potentially be the link between neurological symptoms and immune system dysfunction. However, much more study will be needed to get to the bottom of this relationship.

Similarly, children in the ASD+GI group tended to have lower levels of the protein zonulin, which helps to regulate how permeable the intestinal wall is.

Earlier studies have demonstrated that children with ASD have “leaky” guts, meaning that toxins and undigested food are able to cross from the intestine to the bloodstream.

ASD and gut bacteria

Children with ASD, whether with or without GI symptoms, had different gut flora populations than the TD groups. However, the ASD+GI group also differed from the ASD group.

Interestingly, the researchers noted differences between the ASD+GI and TD+GI children.

“This work opens up interesting new avenues to determine how the microbiome may be driving the mucosal immune response in ASD or whether immune activation drives the microbiome changes. At present we don’t know.”

As mentioned earlier, children with ASD and GI issues tend to display worse behavior than children with ASD but no GI problems. This relationship needs to be explored further.

“This immune activation is not helping these children. It might not be causing autism — we don’t know that yet — but it’s certainly making things worse.”

“It’s a step toward understanding co-morbidities that are present in at least half of children with ASD, and working out which of these children may respond well to certain types of therapies. Although it’s still early, this work suggests we need to find ways to ease inflammation to help these children.”

Research in mice identifies possible mechanism linking autism, intestinal inflammation

Many people with autism spectrum disorders also experience unusual gastrointestinal inflammation, but thus far scientists have not established whether and how those conditions might be linked.

Now, Harvard Medical School and MIT researchers, working with mouse models, may have found the missing link: Infections during pregnancy can lead to high levels of the inflammatory signaling molecule interleukin-17a (IL-17a), which can not only affect brain development in the fetus, but also alter the maternal microbiome in a way that primes the newborn’s immune system for future inflammatory attacks.

In four studies beginning in 2016, it was traced how elevated IL-17a during pregnancy acts on neural receptors in a specific region of the fetal brain to alter circuit development, leading to autism-like behavioral symptoms in mouse models.

IL-17a can also act to alter the trajectory of offspring’s immune system development.

IL-17a can induce autism-like behavioral phenotypes such as social deficits. The same IL-17a in mothers, through changes in the microbiome community, produces comorbid symptoms in the offspring, specifically a primed immune system.

While the study findings are yet to be confirmed in humans, they do offer a hint that central nervous and immune system problems in individuals with autism-spectrum disorders share an environmental driver: maternal infection during pregnancy.

There has been no mechanistic understanding of why patients with a neurodevelopmental disorder have dysregulated immune system.
"With the new findings, we’ve tied these fragmented links together. It may be that the reason is that they were exposed to this increase in inflammation during pregnancy."

“Thus, increase in IL-17a in moms during pregnancy leads to susceptibility to produce more IL-17a in offspring upon an immune challenge.”

Having established that the immune system of the offspring can become dysregulated by exposure to the mother’s altered microbiome as a result of infection during pregnancy, the remaining question was how that microbiome becomes altered in the first place.

Suspecting IL-17a, the team tested the effects of antibodies that block the cytokine. When they blocked IL-17a in pregnant mice prior to immune activation, their offspring did not exhibit the intestinal inflammation later in life. This also held true when the researchers repeated the experiment of transplanting MIA stool to germ-free mice, this time including stool from pregnant MIA mice with IL-17a blockers. Again, blocking IL-17a amid maternal infection led to a microbiome that did not improperly prime the immune system of offspring.

The results highlight how environmental exposures during pregnancy, such as infection, could have long-term health consequences for the offspring.

Now we know there is indeed a link between intestinal diseases and autism, you probably feel the need for practical advice.

 

Leaky gut and how it affects health and autism symptoms

Leaky gut, also known as increased intestinal permeability, is a digestive disorder that develops when tight junctions loosen or become damaged, allowing undigested food, bacteria, or toxins to leak through the wall of the intestine.

Tight junctions are small gaps in the intestinal lining that promote the transfer of nutrients while preventing undesirable compounds from passing through the intestinal tract into the bloodstream.

Unfortunately, when tight junctions loosen, harmful substances begin to accumulate in the bloodstream, and this may cause various types of inflammatory issues.

In addition to inflammation, symptoms such as food sensitivities, bloating, gas, cramps, and additional digestive problems may develop as a result of a leaky gut.

Although some healthcare providers do not consider leaky gut to be an actual medical diagnosis, mounting scientific evidence indicates this is a true condition that affects many people and may be associated with the onset of numerous health problems such as allergies, asthma, skin disorders, and chronic fatigue syndrome (CFS), among other issues.

Probiotics and autism

Furthermore, many children with attention deficit hyperactivity disorder (ADHD), autism, and other forms of developmental delays tend to suffer from digestive issues, including leaky gut.

One of the main reasons mental health is linked to digestive health is because, in addition to playing a role in the transfer of essential nutrients to the brain, the lining of the intestinal tract is comprised of numerous nerves and beneficial gut bacteria that also support optimal cognitive function.

However, to promote proper nutrient transport to the brain, the intestinal environment must be healthy. Leaky gut causes harmful substances to damage the intestinal lining, and this disrupts normal digestive function. Similarly, if nerves in the gut become inflamed or damaged due to leaky gut, then the transfer of nerve signals that influence mental performance will also be negatively impacted. Therefore, a leaky gut can worsen the symptoms of ADHD and autism.

The development of a leaky gut is associated with a number of factors such as bacterial or candida (yeast) overgrowth in the gut, taking certain medications, and eating inflammatory or gut-irritating foods. However, two of the main triggers are bacterial overgrowth and gluten intake because they enhance the production of a protein called zonulin.

As zonulin levels increase, tight junctions gradually begin to loosen and this causes harmful substances to pass into the bloodstream; the immune system becomes overactive, and it causes children to experience intestinal discomfort.

There are several strategies that help target leaky gut symptoms in children with ADHD or autism. The first strategy involves eliminating food that irritates the gut or causes inflammation. These include:

• gluten-based food, as this protein is hard to digest and is a common allergen
• dairy products, as some children are intolerant to casein (milk protein)
• corn, soy, and eggs, as are also common allergens

Eliminating these foods from the diet helps promote natural healing of the intestinal tract, which can be especially beneficial for children with autism or ADHD.

Micronutrients and probiotic supplementation also foster a healthier intestinal environment. Research shows that this type of supplementation helps improve behavior in children with developmental delays. Micronutrient supplementation addresses nutritional deficiencies that may be contributing to cognitive impairments.

Probiotics improve digestive function by enhancing nutrient absorption, targeting harmful bacteria that cause intestinal inflammation, and releasing enzymes that heighten the digestion of food. The combination of these strategies targets the leaky gut by supporting the restoration of proper tight junction function. This can improve intestinal and cognitive health for children with autism and ADHD.