As I've mentioned in other posts, scientists have to read about and understand the current scientific literature. Lots of the time this is done alone, at your desk in the office or the lab, for hours and hours so that you can really understand whatever topic it is that you're studying. But one of my favorite ways to share scientific papers is through a weekly meeting with the whole lab called a Journal Club. Although my husband laughs about this kind of nerdy science "club" (akin to his amusement about scientific societies), it's a great way to discuss a particular topic and dive deep into a discussion about how the researchers got their results and came to their conclusions. This is the first of many Journal Clubs where we will do an abbreviated version of what we would discuss in a typical journal club in the lab.
Paper TItle: Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children
Authors: Dae-Wook Kang , Jin Gyoon Park ,Zehra Esra Ilhan, Garrick Wallstrom, Joshua LaBaer, James B. Adams, Rosa Krajmalnik-Brown
Full disclosure, Dr. LaBaer is the Director of the center I previously worked in at the Biodesign Institute at ASU. Drs. Park and Wallstrom worked in offices down the hall from me and Dr. Krajmalnik-Brown was in another center at the Biodesign Institute.
Journal: PLOS One (PLOS stands for "Public Library of Science"). In case you want to read the whole article, it can be downloaded (for free) here
Background/Introduction: Before this paper was published, scientists knew that many children with autism also had gastrointestinal (GI) issues suggesting that there may be a connection between the two. There have been some studies looking at antibiotic treatment (which could change the gut microbiome) before 3 years of age and how this might be connected with autism. There have also been studies connecting the gut microbiome and the brain. So there was evidence that the gut microbiome and autism may be related in some way.
When this paper was written, scientists also knew about the microbiome and how changes in the bacteria (all 1,000,000,000,000,000 of them) that are in the gut are found in patients with many different diseases - from C. diff infection to obesity to depression.
Goal of this paper: Look closely at the changes in the gut microbiome of children with autism to better understand how these two might be related.
Methods/what did they do?: Bacteria in fecal samples is considered representative of bacteria in the gut microbiome. Therefore, the researchers collected fecal samples from children both with (20 children) and without (20 children) autism. The samples from patients without autism were used as a "control" to compare to the autistic samples. The researchers also asked the children (or their parents) questions to help determine the level of GI issues, the severity of their autism, and their environmental factors like their diet. The researchers isolated bacterial DNA from each of these fecal samples and then sequenced the DNA to determine what types of bacteria are in the gut.
Results: Through sequence analysis and other statistical methods, the authors found that children who did not have autism have a more diverse microbiome compared to autistic children. If there is higher diversity, it means that the gut contains more different types of bacteria, and lower diversity means a smaller variety of bacteria in the gut. They also found that in the autistic patients with a greater diversity in their microbiome, their autism was generally less severe. They also did not find any correlation between age, gender or diet with these microbiome changes.
The scientists also looked at what specific genus and species of bacteria were more represented in non-autistic versus autistic children. Specifically the bacteria from genus Veillonellacaea, Provetella, and Coprococcus are less abundant in autistic children.
Discussion/Significance: What does this all mean? The researchers did find a correlation between decreased gut microbiome diversity and autism. It should be clarified that just because GI problems are often found in autistic children and the severity of the GI issues correlates with the severity of autism, this does not necessarily mean that GI issues cause autism or vice versa. That still needs to be determined. Also because the diversity of bacteria in autistic children is low, it is not clear if this is a cause of autism or an effect of a child having autism. However, this paper does provide a "stepping stone" to better understand what is happening in the gut of autistic children and may help define a target for diagnosing autism (by looking at the decreased diversity in the gut as a diagnostic test) or treatment (perhaps through fecal transplant).
What has been done since? This paper was published in 2013. So what has changed since the paper was published? Do we know whether or not changes in the gut microbiome cause autism or not? Unfortunately, this is still unclear. However, if these microbiome changes are a cause of the neurological changes in autism, then one would want to do a clinical trial to test what happens to autism symptoms when the microbiome has been altered. This could be done in a number ways including diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal.
Researchers have started this process by holding a meeting that included patients and their families to figure out how this type of trial could be designed (for more details, check out this journal article).
Dr. Cathy Seiler is the Program Manager for the tissue biorepository at St. Joseph's Hospital and Barrow Neurological Institute. She has her BA in Biochemistry and Molecular Biology from Boston University and PhD in the Biological Sciences from Cold Spring Harbor Laboratory. Her research and teaching focuses on genetics, cancer, and personalized medicine. Find her on Facebook at www.facebook.com/thingsitellmymom