Last week I had an animated discussion on Facebook over an older post in which I describe some literature I dug out on possible (underline “possible”!) correlations with autism. True, my post is highly incomplete, but it was meant as a discussion starter to point at things that scientists have been looking at in an attempt to unravel what feels like a rise in autism. Is autism the new childhood plague of our modern society or has it always been around and we just became more aware of it? And if the rise is real, what caused it?
To me the most intriguing bit is that if you type 'autism gut microbiota' into the PubMed search field (for those not familiar with PubMed, it's a repository for medical literature), you find an incredible number of studies and reviews: apparently there is an association between autism and disruptions of the gut microbiota, but whether the two are truly correlated or the correlation is spurious is still unclear.
Before I go on analyzing the literature I found on this topic, let me open a parenthesis on the Facebook discussion because it's something I deeply care about. You might think that the animated discussion I got into was with anti-vaxxers who believe that vaccines cause autism. Instead, my post was criticized by pro-vaccine people who, with the same unflinching certainty typical of the anti-vaxxers, believe that the rise in autism is fiction invented by anti-vaxxers, that autism has always been around, and that any difference between gut microbiota of autistic children and non-autistic children has been disproved. "By whom?" I asked. By this one report:
"Children with autism have no unique pattern of abnormal results on endoscopy or other tests for gastrointestinal (GI) disorders, compared to non-autistic children with GI symptoms, reports a study in the Journal of Pediatric Gastroenterology and Nutrition."Notice that this opening line is a bit misleading because here is the actual paper  whose conclusion, quoting from the abstract, are a bit more cautiously stated:
"This study supports the observation that children with autism who have symptoms of gastrointestinal disorders have objective findings similar to children without autism. Neither non-invasive testing nor endoscopic findings identify gastrointestinal pathology specific to autism, but may be of benefit in identifying children with autism who have atypical symptoms."Notice also the difference from the abstract and the title of the report. You can tell which one was written by a scientist, right? Because when you do a search on PubMed using keywords autism and gut microbiota you find a long list of references and decades of research. So to me what this says is that the question is still open and we need to understand the issues better. It takes way more than one paper to disprove hypothesis-raising questions spurred from decades of research.
Now here's the mother of all problems: the Internet has made everyone (EVERYONE!) an expert. Today you no longer need a medical degree to speak authoritatively about vaccines, disease, and health. This has generated movements like the anti-vaxxers, but, even more unfortunate is the rise of groups that reply to the anti-vaxxers without a scientific mind-set: these people are doing even more damage to the community than the anti-vaxxers themselves. I found myself in a conversation that had the same one-ended arguments used by anti-vaxxers except these were people who are actually in favor of vaccines: for every paper on autism and gut microbiota I brought up they would dismiss it with another one that said the opposite, demonstrating no understanding of the difference between raising hypotheses and making a claim.
As a scientist, I can tell you that this behavior is the very opposite of scientific thinking. All the people who are in favor of science but DO NOT adopt a scientific attitude when counter-arguing non-scientific claims are hurting the scientific community. It's happening for vaccines, for evolution, and for global warming. For example, people who support intelligent design are mistaken about evolution because they don't understand the meaning of the word "theory" and they don't understand how scientific thinking works. We need to educate people on scientific thinking, not give bad examples of undebatable and absolute notions.
So, PLEASE, all science fans, I beg of you: support us by giving us a cheer, by always citing original papers, and by keeping an open mind because that's what a real scientist would do. We are raising hypotheses, not discussing the meaning of Bible verses. And if you know you can't do any of the above, then the best support you can give us is to shut up. Let real science speak for itself.
I'm fully aware that I'm preaching to the choir so I'll stop now and resume my discussion on autism and gut microbiota. As an additional side note, let me emphasize how difficult it is to discuss a topic like autism because of its extreme complexity: it's a relatively new diagnosis (first described in the early twentieth century), and even though no exact etiology has been found of date, the genetic studies conducted so far have implicated as many as 400 genes such that a malfunction in any of these genes could possibly result in autism .
Let's start from the facts: our body hosts more microbial cells than human cells, with the vast majority residing in the gut. These organisms, which we collectively call the "human microbiota" (and “gut microbiota” when referring to the ones residing in the gut) interact with our cells in symbiosis and in fact, some experiments have shown that they can affect our health and even gene expression (see this old post for a striking example of how genes expressed by gut bacteria can affect whether we are fat or lean). All this has been known for a long time, but it's only recently that, thanks to the advent of new DNA sequencing techniques that scientists have been able to look deeper into the composition and classification of the human microbiota. Metagenomic studies have found over 3 million distinct microbial genes (collectively called the "microbiome") in human stools, which is astonishing if you think that the human genome, in comparison, contains about 20-30 thousand genes. The gut microbiome is rich in enzymes without which our body would be unable to digest important nutrients. In fact, it's estimated that roughly 10% of our dietary energy intake comes from byproducts of fermentation from the gut bacteria.
That's all fine and dandy, but what does this have to do with behavior and brain health? A lot, actually, to the point that scientists coined the phrase "gut-brain axis" to denote the deep interaction between the nervous system and the gut microbiota. A 2011 PNAS study  used a mouse model to demonstrate how the gut microbiota affects mammalian brain development and behavior. This can happen in a number of ways, but one interesting hypothesis is that a healthy gut microbiome can help modulate the concentration of chemicals that are important for brain development as well as important nutrients that are precursors of neurotransmitters like serotonin.
Several studies done on different populations of children affected by autism spectrum disorders (ASD) have reported some form of gastro-intestinal (GI) dysfunction (such as food intolerances, abdominal pain, diarrhea and flatulence), with proportions ranging from 20-60% of the study population . It's true that ASD children are often very picky eaters with drastic dietary habits, which would of course cause the GI issues. However, given the previously mentioned evidence that the gut microbiota shapes brain development since early infancy, the question of which is the cause and which is the effect at this point is legitimate. In other words, what came first, the chicken or the egg?
Studies have pointed at alterations of the gut microbiota in ASD children who experience gastro-intestinal issues, and some have reported that ASD children receiving antibiotics seemed to experience behavioral improvements. Drastic changes in diet (for example adopting a gluten-free and/or casein free diet) have shown behavioral improvements in some ASD studies, but not in all (meaning that some studies still didn't observe any improvement). Some papers report a higher risk of ASD in children who have not been breast-fed or who have been weaned after the first month of life. All of these instances would cause the gut microbiota to change, including breast feeding, which plays a fundamental role in establishing a healthy bacterial flora in infants. But why aren't any of these studies conclusive? And why are some conclusions the opposite of others? Such differences in results can be explained by differences in sample sizes (too few patients, for example, would cause a false negative), and also by the fact that many of these children have impaired communication skills, and therefore the symptoms, rather than being self-reported, are gathered from the observations of the parents, which can potentially introduce a bias.
Studies that have compared the microbial composition of stools in children affected by ASD with healthy children have had mixed results: the majority report some differences in the composition of the microbial populations, while a few found no significant differences. And despite many studies have looked into it, no ASD-specific gut disturbance has been found, meaning that whatever gut issues ASD children may experience, they are no different than the ones healthy children may experience as well. At the same time, there is some evidence that probiotics help relieve some of the gastro-intestinal issues ASD children experience and at the same time, improve some of their behavioral issues.
What conclusion can we draw from this? Well, first of all that there's no black and white but a lot of gray and anyone who will tell you it's either black or white does not understand how science works. Look at Lamarck's theory of the evolution of traits, first dismissed by Darwin and now (sort of) coming back in the form of epigenetics. Science is not a means to get a definitive and absolute truth, rather, it is our drive to keep asking questions in the search for working answers. [On a side note, this is exactly why I do not like certain showmen out there who proclaim themselves scientists just because they promote science "truths"; real science educators should be promoting scientific thinking, instead.] More than once in the history of science we've corrected and generalized theories. That doesn't mean that we were wrong, rather, it means that we've expanded our knowledge and acquired better investigative tools.
Unfortunately we don't have historic data on autism, since the term was first used in the early 1900s and the definition of the disorder has changed over time. This questions whether or not case prevalence has been truly rising over time, or, instead, the rise we're seeing is simply the effect of a more comprehensive diagnosis. Regardless of whether this is true or not, the fact that most cases are reported in industrialized countries raises an important speculation: these are countries that have seen the most drastic dietary changes over the past 100 years and also lifestyle changes in terms of hygiene and use of antibacterial products, both in household items, as well as in livestock farming (and the use of antibiotics in livestock farming has indeed been increasing over the past few decades). There is no denying that dietary changes and increased use in antimicrobial products will affect the bacteria coexisting in our environment. Are these changes significant? Can they be play a role in the rise in autism prevalence? Can they play a role in the etiology of other disease whose prevalence appears to be on the rise, such as asthma, food allergies, and autoimmune disorders?
I do believe that these are legitimate questions that call for a deeper understanding of how our body interacts with the environment, both outside and inside. Throughout time, evolution has provided us with ways to adapt, but such adaptations are slow. Instead, over the past 100 years we've introduced drastic changes both in the environment as well as in our lifestyle in ways that are too fast for our genetic make-up to adapt. Anything concerning humans is complex, layered by multiple interactions between genetics, environment, and behavior. That’s why we need to keep looking and, most importantly, that’s why we need to always keep an open mind on things. Anyone who claims to know the absolute truth has misunderstood what science is about. Fighting bogus facts like the ones brought forth by the anti-vaxxers with analogous “absolute truths” will only reinforce the globally spread misunderstanding of what science is and what function it covers in our path toward understanding the world. The day we stop asking questions because we’ve found all the answers is the day we’ve stopped growing.
 Kushak RI, Buie TM, Murray KF, Newburg DS, Chen C, Nestoridi E, & Winter HS (2016). Evaluation of Intestinal Function in Children with Autism and Gastrointestinal Symptoms. Journal of pediatric gastroenterology and nutrition PMID: 26913756
 Li, Q., & Zhou, J. (2016). The microbiota–gut–brain axis and its potential therapeutic role in autism spectrum disorder Neuroscience DOI: 10.1016/j.neuroscience.2016.03.013
 ￼Heijtz, R., Wang, S., Anuar, F., Qian, Y., Bjorkholm, B., Samuelsson, A., Hibberd, M., Forssberg, H., & Pettersson, S. (2011). Normal gut microbiota modulates brain development and behavior Proceedings of the National Academy of Sciences, 108 (7), 3047-3052 DOI: 10.1073/pnas.1010529108
 Mulle, J., Sharp, W., & Cubells, J. (2013). The Gut Microbiome: A New Frontier in Autism Research Current Psychiatry Reports, 15 (2) DOI: 10.1007/s11920-012-0337-0