Treating Autism

Response to:
Treating autism: Gut bacteria may offer a treatment for autism

https://www.economist.com/science-and-technology/2018/12/08/gut-bacteria-may-offer-a-treatment-for-autism

I have often been asked by many of the parents and caregivers of my patients with Autism Spectrum Disorder (ASD) about using probiotics, supplements of live “good” or “helpful” bacteria, in treating these conditions.  They have seen the wonders of probiotics touted as effective and safe treatments and some even claim to cure autism.  Here’s how I usually respond to these inquiries.  First off, I love it when caregivers and family members actively take part in the care team with me because a collaborative approach to care benefits everyone.  Secondly, I think it is great that people are getting more informed about potential breakthroughs in the science of understanding and treating autism.  There have been breath through findings and promising research being done on the association between gut microbiome and ASD.  However, I would caution that the current data does not support the indiscriminate use of probiotics in treating ASD. In fact, many of the researchers in this field of work frequently conclude in their published articles that probiotics in the treatment of ASD have potential.  It is far from being a panacea.

While it has been three quarters of a century  since ASD was first identified by Leo Kanner, an Austrian-American psychiatrist from Johns Hopkins University in 1943, there is yet no known definitive cause or cure.  The number of cases of ASD continue to surge, with the United Nations estimating that 1-2% of the entire world population falls on the autism spectrum. Additionally, in April 2018, the Centers for Disease Control (CDC) announced that the prevalence of ASD in the US has increased by 15 percent from 2016 go 2018;  1 in 68 children in 2016 to 1 in 59 children in 2018. Furthermore, these statistics don’t even take into account all the associated “costs” to society, communities, families, and individuals to provide proper care and support services for these individuals.

With these astonishing statistics, I can understand the strong desire to find a “silver bullet,” particularly parents and caregivers who, on a day to day basis, have to manage the medical conditions (seizures and gastrointestinal problems), behavioral challenges (aggression, self-harming behaviors, and  repetitive behaviors), and mental conditions (anxiety, attentional difficulties, and depression) that commonly co-occur with ASD.  I am also sympathetic to them for wanting to relieve their loved ones discomfort, distress and suffering. The headlines are filled with exciting promises that probiotics can ameliorate many of these medical, behavioral, and psychiatric symptoms. Take for example the December 2018 article from the Economist “Gut bacteria may offer a treatment for autism,” where it is reported that “introducing a particular bacterium into the guts of mice that display autistic symptoms can abolish some of these symptoms.”  Mauro Costa-Mattioli and his colleagues of Baylor College of Medicine found that when administered Lactobacillus reuteri, a bacteria commonly found in healthy digestive tracts, to mice with autism-like traits, their repetitive behaviors stopped and they began to socialize and communicate more with other mice.  What makes this finding even more enticing is that L. reuteri is widely available and its availability is actually approved by the Food and Drug Administration (but not for treatment of ASD).  A few words of caution before you head off to the health food store to stock up on your supply.

First word of caution.  While the link between the bacterial flora in the gut and ASD is not a recent finding, what we do know on this subject is still rudimentary and has not been well studied in humans.  Since the 1960’s,  our knowledge base on ASD has expanded quite considerably.  The discovery that the types and quantities of bacteria found in individuals with ASD was different from individuals who didn’t have ASD came from examining fecal samples of human beings.  However, many of the studies on probiotics as potential treatment for ASD have been done on animals.  In fact, the knowledge we currently have from six decades of research has mainly come from mice models, including the study mentioned in the Economist article.  It would be too premature to apply these findings to human beings because mouse brains aren’t the same as human brains, and mouse microbiomes, the microorganisms found in the gut, aren’t the same as human microbiomes. What we can take from these preliminary findings is that there is rationale to continue research efforts in this subject area, especially with human subjects.  We are in need of more multi-center, large-sample size, randomized controlled trials.

Caution number two.  The association between the gut and ASD involves many intricate, nuanced and sensitive processes.  Just the mere act of introducing more bacteria back in to the mix can disturb or even disrupt this complex gut-brain axis.  There are millions of neurons in the brain and the gut that comprise a communication system called the gut-brain axis, which allows for bidirectional exchange of information between these two organs.  The body of evidence is increasingly showing that complex functions of the immune, endocrine, and nervous systems involved in the gut-brain axis  participate in the development of ASD.  One theory, the “leaky gut” theory, proposes that there are defects in the barriers of the gastrointestinal tract that allow toxins and bacterial matter to enter the bloodstream, subsequently reaching the brain. What this means is that what happens in the gut will essentially affect brain development and function.  We currently know too little about the entire cascade of events that occur in this axis to safely predict that self-administration of probiotics would result in only positive outcomes without upsetting the balance and inner-workings of the gut-brain axis.

A third point of caution is that even probiotics can be overly used.  We can use our experiences with the discovery of the wonder drug penicillin as a cautionary tale.  Indiscriminate use of antibiotics for all infections, regardless of whether they are of bacterial origin or not, led to widespread antibiotic-resistant bacteria and even the emergence of deadly “superbugs,” like methicillin-resistant Staphylococcus aureus (MRSA). Overuse use of probiotics, just like in the case of antibiotics, could potentially diminish or eliminate their usefulness as a treatment intervention.   Worse yet, it could lead to another “superbug”-like situation where the original problems we were targeting with the treatment become even more difficult to treat.

Final word of caution.  Probiotics are considered dietary supplements and are therefore, not monitored or regulated like medications are by the FDA.  The lack of quality control means that the probiotics on the market are not equal. You may not be getting what you think you are purchasing, or the product may not even contain “live” probiotics in it, or it even be mixed with potentially harmful bacteria. For individuals with cow’s milk allergies, remember that probiotics are cultured from cow’s milk and can cause serious potentially life-threatening allergic reactions.  In the famous words of Forest Gump, “you never know what you’re gonna get.”

However, if you are still intent on giving probiotics, here are a few recommendations I have.  First and foremost, carefully consider the symptoms you are hoping probiotics will improve, such as constipation, diarrhea, abdominal pain, or reflux, for example.  Avoid concentrated supplements and instead try a “probiotic” designated yogurt. Read the label to ensure that amounts of viable microorganisms in the supplement are in the billions. If you don’t see any improvement in symptoms you are monitoring after a couple of weeks, stop the treatment to prevent any potential unwanted negative side effects.

References:

Frye, Slattery, MacFabe, Allen-Vercoe, Parker, Rodakis, Adams, Krajmalnik-Brown, Bolte,Kahler, Jennings, James, Cerniglia & Midtvedt (2015). Approaches to studying and manipulating the enteric microbiome to improve autism symptoms, Microbial Ecology in Health and Disease, 26:1, 26878

Jack, Gilbert & Krajmalnik-Brown, Rosa & Porazinska, Dorota & J Weiss, Sophie & Knight, Rob. (2013). Toward Effective Probiotics for Autism and Other Neurodevelopmental Disorders. Cell. 155. 1446-8. 10.1016/j.cell.2013.11.035.

Mulle, Sharp, & Cubells (2013). The gut microbiome: a new frontier in autism research. Current psychiatry reports, 15(2), 337.

Navarro, Liu, & Rhoads(2016). Can probiotics benefit children with autism spectrum disorders?. World journal of gastroenterology, 22(46), 10093-10102.