Role of the Gut Microbiota in Autism Spectrum Disorders and Inflammatory Bowel Diseases (QNRF grant - UREP21-059-1-011).

Background
I am a Neuroscientist. Yet, I am fascinated by the Gut and how the Gut can control the brain. To be sincere, I wasn't interested in Autism at first. I was more interested into why people with inflammatory bowel diseases are often asked teh question "are you stressed"? That's what a doctor told me after they've discovered I had Crohn's disease.  I was curious to understand why most people with a gastrointestinal disease or disorder also have anxiety disorders, and interestingly those who have anxiety disorders like Autism or Attention Deficit Hyperactivity Disorder, often have gastrointestinal problems. Thousands of studies have been performed on Autism and how it relates to what we call the Gut Microbiota, those microbes living in our guts. However none of these studies were done in the Middle East, a region were Autism is in the rise.  In 2017, I was was awarded a grant, my first research grant, to study Autism and the microbial theory. This project won the first prize of the 12th annual UREP competition, because of its impact and resulted in the publication of 3 reviews, 2 original articles. 

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English Public Summary
Click here for the Arabic Summary

When I launched this clinical study in Qatar in 2017, I remember I told my colleague: “I just want people to know”.
Well, almost 5 years later, we have run the study, we have published 5 publications, and still when I talk about fecal transplant or gut microbes in Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorders (ADHD), people give me the impression that I am talking about something new.
No, it is not new. Dysbiosis, or the alteration in the diversity and abundance of the gut microbial communities, has been consistently linked to modern diseases such as metabolic diseases, neurodegenerative diseases, cancers, autoimmune diseases, and even neuropsychiatric and neurodevelopmental disorders such as ASD or ADHD. In fact, I have designed my study just to confirm the observations made by other scientists worldwide, and we did.
The problem is that the language scientists use to publish is not comprehensible by everyone.
Therefore, I am putting here this summary of what I think are key for people to know and understand regarding what’s going on between ASD, ADHD and IBD and lifestyle.
 
The study involved 55 participants who had either ASD or ADHD or IBS (inflammatory bowel syndrome) or IBD (Inflammatory bowel disease) or none of these (controls).
We recruited participants via flyers on social media and via the Child Development Center (Doha, Qatar) as well. https://www.mdpi.com/2076-2607/9/4/741/htm
 
Participants filled a questionnaire about their lifestyle including their milk consumption, the exposure to antibiotics before age of 3, their consumption of probiotics, and processed grain-based products. Then we have offered them a collection kit for them to collect a stool sample for us at home, which we collected afterwards. We stored the stool samples in a very cold freezer (-80 C) until analysis.
 
I had 6 students working with me on this project and two colleagues, on immunologist. Dr. Dalia Zakaria and one biostatistician, Dr. Noha Yousri. I can tell you that some of my students had quite interesting experience while extracting DNA from stool samples. So, what were we looking for?
The question is simple: most ASD kids tend to also have gastrointestinal disorders, and in the other hand, most people with an IBD also suffer from some level of anxiety or also have ADHD, in which direction is this working? Are the two related?
According to previous studies, yes. The observation that many studies have done before us is that microbes in the gut, if not in equilibrium, will lose the ability to maintain an impermeable gut wall. This means that gut becomes leaky. And if the gut is leaky, not only toxins can enter your body via the blood vessels around your gut, but allergens contained in the food you eat can easily go through.  Another important function for these microbes is that, with their diversity, they are able to control each other’s growth and prevent the overgrowth of pathogens, which otherwise can produce toxins that reach your organs, including your brain.
Finally, these microbes trigger the production of molecules that communicate with many of your organs, including your brain. Therefore, having a very diverse gut microbiome is extremely important, and studies have noticed that people with chronic diseases or disorders often have very low diversity of gut microbes. Some have even noticed the overgrowth of certain specific bacteria.
So, we wanted to see if in our samples we could observe this decrease in diversity. The answer was yes: diversity of microbes significantly decreased in both the ASD/ADHD group and the in the IBD/IBS group compared to the healthy people, but it decreased much more in the ASD/ADHD group than in people with gastrointestinal issues mainly.
 
What is interesting here is that in our study, not only we looked at bacteria, but also as fungi (the kingdom which mushrooms belong to). And here is the big discovery, because very little studies have included Fungi in their investigations: we found that one specific fungus, saccharomyces cerevisiae, increased in abundance in the ASD/ADHD group, as if the decrease in diversity of bacteria allowed this fungus to grow. And guess what this fungus needs the most to grow? Sugar.
 
Sometimes I meet with parents of kids who have ASD complaining that their child is craving sugar. Well, he surely will because of this microbes. But removing sugar is a must in this case in order to reestablish equilibrium in the gut.
Another important point we have observed through our investigation is that 58% of the ASD/ADHD group were exposed to several courses of antibiotics before 3 years old (against 21% in the healthy controls, and 39% in the IBD/IBS group), this was statistically significant. https://pubmed.ncbi.nlm.nih.gov/33598417/
And for those who want to say that our sample size was small, please visit the study of Slob et al. [35] which explicitly showed, in a cohort of 27,781 twins, that early exposure to antibiotics significantly increased the risk of developing ADHD and ASD. Again, I am not saying anything new, our study just confirmed other observations made previously.
In addition, we noticed that antibiotics exposure seems to be associated with more fungal dysbiosis than bacterial dysbiosis. https://www.mdpi.com/2076-2607/9/4/741/htm
 
With this study, we managed to show that Fungi are important to include in studies, as they might be key in differentiating between people who have ASD with an IBD and those who have and IBD with some anxiety or attention disorders.
 
Now you can probably understand why I am talking about fecal transplants. This practice is also not new, it has been practiced for thousands of years by humans. Today, scientists are considering this technique to re-inject diversity in the gut of people who have lost it (as a result of their lifestyle). Is it safe? Knowing how little we know about microbes’ interactions, not really. But it can work. https://www.qscience.com/content/journals/10.5339/qmj.2021.5
 
A study published in Nature, one of the scientific journals with most impact, showed that the fecal transplant in children with autism can have long term benefits such as moving the child across the spectrum, some of them even had no clinical signs of ASD after two years. https://www.nature.com/articles/s41598-019-42183-0
 
Researches are still going on, and, in my quality of researcher and Lifestyle Medicine Professional, here are the main key points I suggest you can share:

1. Disease is often linked to low diversity of microbes in the gut.
2. Some microbes are bad, but others are good. Therefore, having more good microbes in the gut helps in establishing an equilibrium and neutralizing the bad effects. Probiotics are a good source of good microbes and they have been shown to improve symptomatology. https://pubmed.ncbi.nlm.nih.gov/32532137/​
3. Recurring courses of antibiotics between 0 and 3 years old have been associated to ASD/ADHD, and some have even showed it can increase the risk of developing these disorders.
4. Sugar and processed-grain-based products are the main enemy for dysbiosis: lifestyle changes can slowly (very slowly… very very slowly) change the microbiome and safely take you back to health.
5. Fecal transplants are the transplant of stool sample from a healthy donor to a person with low gut diversity to repopulate his gut with a set that is in equilibrium. This in itself have saved a lot of lives in the treatment of some bacterial infections, and it is being tried for many disorders and diseases (including IBD, and ASD) with very promising results.