The past several decades have been met with a roaring increase in the discussions surrounding autism and related disorders that fall within the Autism Spectrum. And with good reason.
First coined in 1910, autism quickly emerged as a notoriously difficult condition to diagnose, given its eerie similarity to other neurodevelopment disorders, specifically childhood schizophrenia. Indeed, it took nearly 70 years of intense research for autism to be diagnosed as a separate disorder (2). Since then, autism prevalence has skyrocketed in Western society; prior to 1980, 1 in 5000 children were diagnosed with autism. Today, an astounding 1 in 68 children possess autism-like symptoms, which include limited social interactions, a tendency for repetitive behaviour and reduced overall communication (3).
Which begs us to ask the question: why?
An enormous array of controversial explanations have been put forward to explain the worrying increase in autism prevalence. The most notorious of which is Andrew Wakefield’s “vaccine hypothesis”, which singled-out the MMR vaccine (Measles, Mumps & Rubella) as the cause of rising autism prevalence (note: Wakefield’s findings have since proven to be falsified and have been retracted from the scientific literature. Read more here: (4))
It was only in the mid 1980s that researchers uncovered that autism had a strong genetic component, wherein certain gene mutations were found to associated with autism (5). The genetic basis became even more clear by the 1990s, when it was discovered that a child was 25-times more likely to be diagnosed with autism if one of their siblings was also diagnosed (6). Since then, an impressive amount of research, made possible by advances in genetic technologies, has identified numerous genes linked to autism (which are summarized in this article: (7)).
While genetics undoubtedly play a role in the development of autism, the last decade saw scientists explore an alternative hypothesis — one that included the microbiome. For years, researchers couldn’t explain the seemingly-odd data that showed — quite conclusively — that women who suffered a high, prolonged fever during pregnancy were seven times more likely to have a child with autism. In 2007, Paul Patterson was able to reproduce this result in mice, such that if he induced a prolonged fever in pregnant mice, then their offspring would display all three features of human autism, including limited social interactions, a tendency for repetitive behaviour and reduced overall communication (8). Patterson also showed that the offsprings also had leaky intestines, which is a critical detail here because anywhere from 40 to 90% of human children with autism also suffer gastrointestinal issues (9).
Then, in 2013, Dr. Sarkis Mazmanian and his research team made the remarkable discovery that these mice had abnormal microbiomes compared to non-autistic mice (10). This finding suggested that the autistic-like behaviour of these mice — and perhaps by extension autistic behaviour in humans — might be partially rooted in the gut rather than entirely in the brain.
If this is true, then treating the gut bacteria should also treat the autism-like symptoms. And indeed, Mazmanian’s research team was able to show that by simply restoring a normal microbiota, the mice also displayed better communication and a decreased tendency towards repetitive behaviour. This heavily implicates our gut bacteria as one of the culprits of autism, and — at least in mice — shows that some features of autism can be reversed by treating an abnormal gut microbiome.
There remains one more twist to this story. Earlier, it was mentioned that a sharp rise in autism prevalence was observed at the end of the 1970s. It turns out that the same can be said for obesity. That is, the rates of both autism and obesity among Westerners seem to have taken off around the same time — the end of the 1970s. This may seem like a simple coincidence (and it very well might be) but consider this: it was during the 1970s that Westerns began to adopt a diet rich in processed foods, sugar-sweetened drinks and a mostly sedentary lifestyle (11). That’s important here because, as we have spoken about in previous blogs, it’s already very well appreciated that our gut bacteria influence our weight (You can read that blog here: http://www.thegutguys.com/myhealth/category/obesity).
Given that our gut bacteria have already been shown to influence weight, and given that autism prevalence spiked once the Western diet was introduced in the late 1970s, is it too far-fetched to assume that they also contribute to autism? Has our adoption of the Western diet molded a “bad” microbiome conducive to both obesity and autism? Although further research is required to fully understand the answer to that question, it definitely deserves its fair share of discussion, as autism prevalence among our children continues to increase at an alarming rate.
1. Muir, H. 2003. Einstein and Newton showed signs of autism. In New Scientist.
2. Wilson, M. 1993. DSM-III and the transformation of American psychiatry: a history. Am. J. Psychiatry 150: 399-410.
3. Centers for Disease Control and Prevention. 2012. Autism Spectrum Disorder — Data & Statistics.
4. Rao, T. S. S., and C. Andrade. 2011. The MMR vaccine and autism: Sensation, refutation, retraction, and fraud. Indian J. Psychiatry 53: 95-96.
5. Blomquist, H. K., M. Bohman, S. O. Edvinsson, C. Gillberg, K. H. Gustavson, G. Holmgren, and J. Wahlstrom. 1985. Frequency of the fragile X syndrome in infantile autism. A Swedish multicenter study. Clin. Genet. 27: 113-117.
6. Jorde, L. B., S. J. Hasstedt, E. R. Ritvo, A. Mason-Brothers, B. J. Freeman, C. Pingree, W. M. McMahon, B. Petersen, W. R. Jenson, and A. Mo. 1991. Complex segregation analysis of autism. Am. J. Hum. Genet. 49: 932-938.
7. Miles, J. H. 2011. Autism spectrum disorders--a genetics review. Genet. Med. 13: 278-294.
8. Malkova, N. V., C. Z. Yu, E. Y. Hsiao, M. J. Moore, and P. H. Patterson. 2012. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain. Behav. Immun. 26: 607-616.
9. Erickson, C. A., K. A. Stigler, M. R. Corkins, D. J. Posey, J. F. Fitzgerald, and C. J. McDougle. 2005. Gastrointestinal factors in autistic disorder: a critical review. J. Autism Dev. Disord. 35: 713-727.
10. Hsiao, E. Y., S. W. McBride, S. Hsien, G. Sharon, E. R. Hyde, T. McCue, J. A. Codelli, J. Chow, S. E. Reisman, J. F. Petrosino, P. H. Patterson, and S. K. Mazmanian. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155: 1451-1463.
11. Popkin, B. M., L. S. Adair, and S. W. Ng. 2012. NOW AND THEN: The Global Nutrition Transition: The Pandemic of Obesity in Developing Countries. Nutr. Rev. 70: 3-21.
Yup, another early morning class. Well, it’s not all so bad – my nutrition professor is going to discuss which foods we should be eating to maximize our performance during physical activity (verdict: we don’t know… But it’s probably not a bad idea to eat your greens!). Pretty interesting topic right?
I zoned out, AGAIN. Just once I’d like to get through one full lecture with full concentration. Anyways, as I was wandering the recesses of my mind, I stumbled upon a terrific blog idea: How does physical activity impact our gut bacteria and vice-versa?
As mentioned in previous blogs, the gut microbiota plays a crucial role in human health; it prevents the survival of pathogenic bacteria (these critters harm you and can even kill you), stimulates the proliferation of epithelial cells (i.e. the cells that line your intestines and are thus in direct contact with the bacteria living there. Proliferation is a good thing – it allows the lining of the intestines to replenished frequently and remain rejuvenated) (1) and helps to digest certain nutrients that we can’t digest on our own. It’s a love-hate relationship, really; while we require the gut flora to keep us alive and well, an altered gut bacteria has been associated with many diseases such as obesity, heart failures, cancer, and diabetes (see previous blogs).
Now, is there a correlation between physical activity and a healthy gut microbiota?
Many studies have shown that physical activity is associated with a healthy microflora. Studies by Dr. Matsumoto and his colleagues have successfully demonstrated that rats following a rigorous running regimen harbor a different gut microbiome composition than control rats whom refrained from running. This showed that rats who did running exercises had a different microbial composition in the gut (2).
So what? Matsumoto investigated his findings deeper, and found that this exercise-induced microbiome produced high levels of an infamous compound known as “butyrate”. Butyrate has been well characterized as a potent suppressor of both colon cancer and inflammatory bowel disease (2, 3)
A revealing study by CC Evans in 2014 built on Matsumoto’s work. Evans and his colleagues demonstrated (through an elegant set of experiments) that mice were able to counter the obesity-inducing effects of a high-fat diet through exercise alone. “But you already knew that !”
The real interesting finding made by Evans was that as the mice ran for greater distances, the lower their Firmicutes:Bacteroides ratio became in the gut (4). If you’re familiar with our previous blog, then you may remember that a lower ratio correlates with weight loss. Essentially, they showed that exercise played a role in preventing obesity by favoring a bacterial composition that is similar to those in lean mice regardless of the diet.
Although, these studies have shown some promising results, you might be wondering if this applies to human beings.
A study on the “fecal microbiota of individuals with different fitness levels” (5) following similar diets showed that people with a higher cardiorespiratory fitness had a greater microbial diversity in their gut. This study by Estaki et al. demonstrated that people who were more physically active had an increase in gut microbial diversity irrespective of the diet, and that diversity is a potent driver of optimal gut health. Additionally, similar to the study in mice, fit individuals showed an increase in butyrate producing bacteria
How does doing exercise change the microbial diversity in the gut?
Further studies are required to fully comprehend the mechanism by which exercise changes the composition of gut bacteria. Nevertheless, one possible theory is that exercise causes lactic acid to be produced in the body, which could be converted by certain bacteria in the gut to butyrate (6).
So if you didn’t already have enough reasons to get to the gym, here’s one more: these studies demonstrate the potential of exercise to be used as a treatment to restore a healthy gut microbiota. We can, quite literally, run our way to a better microbiome.
1. S. Rakoff-Nahoum, J. Paglino, F. Eslami-Varzaneh, S. Edberg, and R. Medzhitov, “Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis,” Cell, vol. 118, no. 2, pp. 229–241, 2004.
2. M. Matsumoto, R. Inoue, T. Tsukahara et al., “Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum,” Bioscience, Biotechnology, and Biochemistry, vol. 72, no. 2, pp. 572–576, 2008.
3. Tan, Hwee Tong, Sandra Tan, Qingsong Lin, Teck Kwang Lim, Choy Leong Hew, and Maxey C. M. Chung. "Quantitative and Temporal Proteome Analysis of Butyrate-treated Colorectal Cancer Cells." Molecular & Cellular Proteomics 7.6 (2008): 1174-185. Web.
4. C. C. Evans, K. J. LePard, J. W. Kwak et al., “Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity,” PLoS ONE, vol. 9, no. 3, Article ID e92193, 2014.
5. M. Estaki, J. Pither, P. Baumeister et al., “Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions,” The FASEB Journal, vol. 30, no. 1, pp. 1027–1035, 2016.
6. S. H. Duncan, P. Louis, and H. J. Flint, “Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product,” Applied and Environmental Microbiology, vol. 70, no. 10, pp. 5810–5817, 2004.