The Fascinating Connection Between Autism and the Bacteria in our Gut

It has become virtually impossible these days to find anyone who is not personally if not indirectly touched by autism in one way or the other.

The dramatically rising rates of autism rates constitute nothing short of a public health crisis. In the 1970’s and 1980’s the diagnosis rate was one out of every 2,000 children in the US. Now, the US Center for Disease Control (CDC) has estimated that one out of every 68 children in the US has been affected by Autism Spectrum Disorder (ASD). ASD includes not only autism, but also Asperger’s syndrome and pervasive developmental disorder. The United Nations believes that 70 million people worldwide are on the autism spectrum. In children, the disease’s prevalence exceeds those affected by diabetes, cancer and AIDS, combined.

While a share of this increase can certainly be attributed to expanded diagnosis criteria and increased public awareness leading higher rates of diagnosis than in the recent past, the dramatic surge in ASD is likely much more than simply increases in detection or over-diagnosis. Indeed, more families are being impacted by autism than ever before.

It is devastating for families when a child cannot fully participate in typical childhood activities or may not be able to achieve independence in adulthood. Beyond the emotional and social challenges faced by individuals and families, the high rates of ASD have alarming implications for society, both in terms of financial resources spent treating and caring for affected individuals and also the loss of workforce productivity that results when parents are forced to reduce work schedules to care for their children. If the one in 68 statistic is even close to accurate, the impact is massive.

Currently, there is no known cause or cure for autism although there are some promising developments in autism research. The disease is complex, and doctors believe it involves both genetic and environmental causes. Trying to determine what is triggering its dramatic surge is at the forefront of much autism research and thus far, no definitive answers have been identified.

Somewhat surprisingly, since autism seems like a disease of the brain, the microbiome (the microbes that live in the digestive tract) is one of the most promising and fruitful areas for ongoing research into the causes of ASD and therapies aimed at improving its symptoms. “Several lines of research … point to the possibility that changes in the gut either cause or are highly associated with driving core ASD (autism spectrum disorder) symptoms,” states Dr. Richard E. Frye, Director of Arkansas Children’s Hospital (ACH) autism research program. Efforts now are focused at designing controlled experiments and raising the funds necessary to conduct research into the autism-gut connection.

The Mind-Gut Connection

Powerful Link between the Gut and the Brain

There is a close connection between the gut and the brain. Researchers have come to find out that the gut microbiome can powerfully affect our minds and influence our behavior and emotions in significant ways. The microbial mix in our digestive tract can influence feelings of depression and anxiety. Our gut microbiome can influence appetite, metabolism and even cause a propensity toward obesity or leanness. The gut microbiome also influences infant brain development, which then has a powerful influence on health and well-being even in adulthood.

Communication between our guts and our brains happens through three channels.

First, the immune system, a large part of which resides in the gut, impacts brain functioning and vice versa.

Second, the enteric nervous system (referred to as our “second brain”) is a network of 100 million neurons in our digestive tract. The enteric nervous system is connected to the brain via the vagus nerve. The vagus nerve provides a pathway for the digestive tract and the brain to communicate and influence each other, controlling digestion and creating feelings of hunger, satiety, food cravings and even emotion. Some scientists theorize that it is disturbances to the enteric system (that is found in the gut) that cause autism.

Third, microbes themselves produce neurotransmitters, many of which are the same ones produced by our cells, which travel to the brain in the blood. Which microbes reside in the gut will affect which psychoactive chemicals are produced and what messages are received by the brain.

Experiments in mice show promise that microbes can change behaviors. Different strains of mice have known differences in behavior. There are also documented differences in the microbial communities in the guts among the different strains. Mice that were specially bred in a microbe free environment were later exposed to different microbes found these other strains. Amazingly the formerly germ-free mice’s behavior changed to correspond to whichever strain of mice the transplant came from.

Children with ASD Often Have Different Gut Composition

The large majority of children with ASD have gastrointestinal disturbances. Their microbiomes typically have fewer overall microbes and smaller numbers of health-promoting microbes than their neuro-typical peers. Biologists believe that diversity of gut bacteria species is an important marker for health.

Increased Rates of Gastrointestinal Disorder in ASD

Gastrointestinal problems are one of the most common health concerns afflicting autistic children – up to 90% of them suffer from gut disorders including “leaky gut” (where intestines become permeable enough that their contents leak into the body) and inflammatory bowel disease. Children with autism have a 350% increased likelihood to suffer from diarrhea and / or constipation than those without it. The gastrointestinal concerns typically do not resolve once the child affected by ASD reaches adulthood.

Differing Microbiomes with Reduced Microbial Diversity

Ongoing comparisons of the gut microbiomes (the community comprised of trillions of bacteria and yeasts living in the digestive tract) of children have revealed dramatic differences in the composition of microbes found in children on the autism spectrum and neuro-typical children. Arizona State researchers who conducted a comprehensive analysis of the microbes found in fecal specimens from both groups determined that children with ASD had many fewer species of bacteria in their gut.

Researchers noted that there were significant differences in the levels of 50 different bacterial species between the two groups. Prevotella copri was the most noticeably reduced species seen in the children with ASD. This is significant because Prevotella copri is typically found in high numbers in neurologically typical children and it is considered to be a health-promoting inhabitant of a well-functioning gut microbiome. They also had lowered counts of Bifidobacterium, a species that is known to provide many health benefits when found in high numbers in the gut.

Clostridia and Ruminococcus bacteria have been found in higher percentages in children with ASD than is expected in a healthy microbiome, particularly in late-onset (regressive-type) autism.

Interestingly, Clostridia bacteria produce propionic acid, as do some other bacteria species. When propionic acid was given to adult rats in an experimental setting, the rats engaged in autistic-like behaviors. These behaviors were reversible meaning they stopped when the proprionic acid was no longer given. Clostridia tend to increase in the digestive tract following a round of antibiotics.

Antibiotics are known disrupters to a healthy gut that can kill off large numbers of health-promoting bacteria in addition to their intended purpose of killing the disease-causing microbes. Reducing the numbers of healthy bacteria in the gut then permits other antibiotic-resistant microbes that they normally keep at bay to flourish.

Could the Microbial Imbalances Cause the Autism Symptoms?

We know that microbes, with their ability to “speak “directly to the brain can affect behavior by influencing mood, emotion and stress levels. We also know that children with ASD have different microbes living in their digestive tract than their neuro-typical peers. This suggests the possibility that the microbial differences in children with ASD are somehow contributing to behaviors that are associated with ASD. If this is so, this leads to the intriguing prospect that perhaps altering the microbiome could improve some distressing behaviors to increase the quality of life for affected children.

However, correlation does not equal causation, meaning just because we see altered microbiomes at much higher rates in children on the autism spectrum does not mean that changes to the microbiome are causing the autism. It could in fact be that somehow the autism or behaviors that go along with it (such as picky eating, for example) could be affecting the gut microbiome. Or perhaps some unrelated third factor is causing both.

Figuring out whether there is a causal relationship is very important, because if there is, this will bring medical researchers one step closer to developing therapies. Knowing one cause of the neurological impairment can helps to focus areas to look into for effective therapies and even cures.

Experiments with “Autistic” Lab Rats

Dr. Elaine Hsiao, a Caltech researcher, bred a line of mice that had autistic-like behaviors by exposing their pregnant mother to a particular flu virus during pregnancy (previous studies showed that getting the flu in pregnancy double a mother’s risk of giving birth to a child with ASD). In mice these behaviors include excessive grooming, anxiety and aloofness. These specially-bred mouse pups went on to develop leaky gut – a condition where the lining of the digestive tract becomes permeable, allowing contents of the gut to seep into the body where they can cause inflammation and other problems. When tested, the mouse babies had 46 times more 4EPS, a molecule produced by gut bacteria, in their blood than the control group of mice that were not bred to show behaviors consistent with ASD. This is significant because a similar chemical has been seen in high levels in the blood of humans with ASD.

Hsiao then supplemented the mouse food with B. fragilis, a probiotic bacteria that has been shown to be effective in treating gut disorders in laboratory mice. Amazingly, the levels blood levels of 4EPS in the experimental group dropped dramatically, their guts became less leaky, and their behaviors changed. The treated mice displayed fewer anxious behaviors. Repetitive activities decreased (obsessively burying a marble) and they became more vocal. Unfortunately, however, following treatment their sociability did not increase when a new mouse was introduced into the cage.

Although the fact that the B. fragilis-treated mouse pup subjects did not show an increase in sociability is a discouraging finding, given that disturbance to social interaction is a hallmark concern for children with ASD, further investigation may reveal that probiotic intervention earlier in the mouse’s life when the nervous system is still newly developing or with different species of bacteria may yield more promising results.

Researchers do not yet understand how gut bacteria influence autistic behavior, but one theory proposed by Dr. Hsiao and her colleagues is that the permeable or leaky gut they can create then permits harmful substances to get to the brain and damage it. If that theory is valid, then it is reasonable to think that introducing microbes into the gut that promote gut health (and reduce gut permeability) could prevent further brain damage.

Hsiao’s results are exciting and provide some hope for improved quality of life for autistic children, particularly if the follow-up studies designed for human subjects show promising results. Designing studies for humans pose challenges, though, as it is not ethical to try to trigger autism in infants as was done with the mice. Further, it may be that probiotic treatment for people would only be effective at a certain very early stage of development, and this might occur before an infant is even identified as having ASD. Therefore, the experimental group would need to include pregnant women who are at risk of having a child with ASD who are willing to agree to participate. Relatively large groups of such women would be necessary as both an experimental and control group would be necessary to obtain statistical meaningful results. This will take money, manpower and time.

Probiotics and Children with ASD

Anecdotally, many parents believe that they were able to “recover” their children from autistic symptoms by making dietary changes aimed at improving gut health, providing high doses of fermented foods that are a very effective way of delivering probiotics and by reducing sugars and carbohydrates that yeasts thrive on. A whole cottage industry has subsequently sprung up around these claims with probiotic bills specially formulated for autism and special diets created just for this purpose.

Other parents have even gone so far as to give their child a fecal transplant in the hopes of improving gut disorders underlying autism symptoms.

Unfortunately, personal experiences are all that we have at this point. I am unaware of any peer reviewed research that has been published on altering the microbial mix in children with ASD. However, research into the microbiome autism connection is underway now.

What Does this Mean for Parents?

Given where the research is thus far – in its infancy – microbiology does not have much specific advice to offer in terms of definitive answers for the parents of children at risk for ASD. Even though microbes have shown promise in rodent studies in the lab, research has a long way to go before identifying which species of probiotic bacteria, if any, are most helpful for people in the real world.

As exciting and promising this area of research is in terms of understanding autism and developing treatments – the gut-autism research is unlikely to provide a silver bullet cure for the disease.

Given that autism is a complex, multi-factorial condition, altering the microbiome to cure the gut, even if it is show to help in an experimental setting, will likely improve bothersome autism-related behavior in only a subset of patients with ASD.

Furthermore, even for those whose ASD does at least partially stem from gut disturbances, it appears likely that treatment would be most effective if provided prior to the critical neurological developmental windows when important brain structures are formed – and unfortunately, these windows may arise before an ASD diagnosis is made. By the time the ASD is identified medically, the window may have passed and the best chance for treatment having faded with it. Animal studies done to date seem to suggest that although bacterial treatments can provide a reduction in certain kinds of ASD behaviors, behaviors such as sociability may not be increased by altering the microbiome, perhaps because of these developmental windows.

It is possible that if gut-related ASD treatments, if and when they are identified, can be undertaken very early in a baby’s life, prior to the critical windows, the behavioral improvements might be more dramatic. Such treatments might be targeted at infants who have been identified as being at risk for ASD, even though they themselves have not yet been diagnosed.

Notwithstanding our current limited understanding of the microbiome-ASD link, improving gut health can offer some immediate relief. For a child with ASD, the sometimes severe discomfort that goes along with chronic and severe gut disturbances such as constipation or diarrhea can get in the way of his being able to fully participate in their therapies and education. Improving gut health in cases like these can make them more comfortable and thereby improve focus and learning while simultaneously reducing ASD behaviors that are exacerbated by distress. This may reduce the impact of the ASD symptoms – even if the microbiome related therapies don’t directly impact the ASD itself.

Given that there are things that all of us can easily do to improve gut health for our children and ourselves without needing a prescription or exposing them to any risky interventions, there seems to be very little risk and potentially great reward undertaking these measures. Gut health is a good thing for everyone.

Baby’s Microbiome

We, as parents, can take steps to assist our infants to develop a healthy microbiome. [Click on this link to find out more about what a baby’s microbiome is and why expectant mothers should care.]

In utero, babies are mostly germ-free. The microbial colonization begins when the baby is swathed in microbes as she makes her slow passage down the birth canal. An expectant mother’s vaginal microbiome actually changes during pregnancy and becomes high in microbes that are beneficial to the baby. Later on, with breastfeeding a mother gives her infant another major contribution of healthy microbes to colonize its developing microbiome. If a woman takes care of her microbiome when pregnant, this can increase the health of the microbial community to be passed to her infant.

Birth via cesarean section or insufficient breast feeding can impact which microbes go on to colonize an infant’s gut and can impact later gut health. Although no causal relationship has been proven, it is interesting to note that children with ASD are more likely than their neuro-typical peers to have been born via C. section and / or to have not been breastfed (or only breastfed for a short duration). Researchers in this area theorize that these factors may lead to an atypical colonization in an infant’s gut microbiome that can trigger developmental problems, such as autism.

Antibiotics are another potential disrupter to the formation of a heathy microbiome in a baby’s digestive tract. An infant’s microbiome is developing and unstable for the first several months of life, so an early dose of antibiotics, with its ability to kill beneficial as well as harmful microbes, can alter the formation of the microbiome.

C. sections, antibiotics and infant formula can all save babies’ lives and should be used without hesitation, whenever medically necessary. A nursing mother can improve her baby’s gut health by eating a diet rich in probiotics (fermented foods) and prebiotics (food needed by her healthy gut microbes). This is particularly important if her baby has been born via C. section or had an early dose of antibiotics.

In Childhood

Feeding difficulties and gastro-intestinal problems are very common in children with ASD.

If a child seems to have disordered eating or is suffering with constipation or digestive disorders, parents can consider making dietary changes to encourage healthy microbes in the digestive tract. Choosing prebiotic and probiotic foods can provide relief from the digestive concerns and, may improve ASD behaviors in the cases where digestive problems co-exist with ASD. Although thus far there is not much medical evidence that this will actually make a difference, there is some, and there are more experiments underway. In the meantime there are a myriad of parents who claim that it helped their child. The only downside is the additional cost required to buy fresh, unprocessed groceries.

In cases of extremely fussy eating, which often goes along with ASD, it can be difficult to get a child to eat a gut-health promoting diet. Vegetables, whole grains and fermented foods can be anathema to a child with a limited tolerance for taste and texture. In this case, and with your pediatrician’s approval, probiotic supplementation can be considered. Probiotic drops exist for younger children or children who cannot swallow a pill. Although ASD symptoms may not improve, the picky-eating itself could get better. There is some evidence that probiotics can increase appetite and food tolerance in picky eaters.

It is important, though, to be mindful about taking probiotics indiscriminately. “Probiotics” is a very broad term, encompassing thousands of bacteria and yeasts that provide beneficial effects to humans. Not every probiotic microbe has the same effect and taking a probiotic without knowing what it does in the human body can be ineffective and wasteful at best, or potentially harmful at worst. Also, depending on the type of dysbiosis that may be present, certain particular probiotics will be more beneficial than others. Be sure to coordinate any attempts at supplementation with a gastroenterologist to maximize the chance for success. Choose a good quality probiotic supplement to maximize any potential benefit.

Conclusion

Although we still have a long way to go before this is fully understood, it is conceivable that making changes to the microbiome in children with ASD can not only provide some relief from distressing digestive disturbances but also providing some respite with troubling behaviors that can go along with autism.

For those of you who have personal experience in either altering a child’s diet or using probiotic supplements in an attempt to improve autism symptoms, we would really like to hear from you about your experiences in the comments below.

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