Autism Gastrointestinal

The Gut Microbiome May Clarify Link Between Autism and Gastrointestinal Problems

Clinical care of the autistic individual can be challenging, with a diverse set of comorbidities complicating the management of core deficits. Autism has been defined primarily as a neuro-developmental issue and characterized by impaired communication, limited social engagement and repetitive behaviors. However, an array of other symptoms often accompany these core traits. In particular, gastrointestinal problems appear to be common comorbidities for individuals with an autism spectrum disorder. Research has indicated that gastrointestinal symptoms occur in children with autism at rate 3-4 times higher than seen in those without. Communication deficits that are the hallmark of autism spectrum disorders can confound diagnosis and delay treatment of gastrointestinal distress. In some children, abdominal symptoms may present as a persistent cough, recurrent throat clearing, or even an exacerbation of problem behaviors, such as self harm.

There seems to be a consensus on an association of autism and gastrointestinal problems, but a definitive link between the two has remained elusive. Without clear evidence of a causative underlying pathology, healthcare professionals apply the same standard of care for both autistic and non-autistic patients to address gastrointestinal complaints. This standard typically focuses on symptom management. However, in addition to gastrointestinal problems, research has shown that individuals with an autism spectrum disorder tend to have a contentious relationship with food in general. For many on the autistic spectrum, food allergies, decreased bowel motility, and self-avoidance of certain foods disrupt their nutritional intake.

Now, some researchers have begun exploring the gut microbiome and the bioactive compounds that some bacteria produce through fermentation in the intestine. Their work seeks to elucidate the association between autism and gastrointestinal problems. The gut microbiome is the complex and diverse population of microorganisms that inhabit the human gut and that exist in a mutualistic relationship with its host. This relationship is integral to the health of the gastrointestinal tract but also extends beyond the gut—the gut microbiome interacts with every system in the body through neurologic, immunologic, and endocrine mediators. Our understanding of this complex network is far from complete, but each new piece of evidence brings us closer to therapeutic modalities that leverage this relationship.

The Gut Microbiome – The Forgotten Organ

As a species, humans have coevolved with the gut flora that resides within us. Our physiology is intimately intertwined with the hundreds of different bacteria, viruses, and fungi that call our guts home. Digestion is one of the most basic and influential metabolic processes of human health where this microbiome is involved. Of particular importance is a group of bacteria known as the fermenters. Humans lack the enzyme to break down large carbohydrate molecules. Through the metabolic process of fermentation, these large carbohydrate molecules are converted to smaller molecules, like short chain fatty acids, that may be absorbed. The fiber in our diet—such as that found in fruits, vegetables, legumes and unrefined grains—is indigestible to humans. However, once in the large intestine, this fiber undergoes fermentation by the microorganisms found there. This fermentation not only metabolizes these non-digestible carbohydrates into nutrients that will support the microbiome, but the products of this metabolism—short chain fatty acids like butyrate, propionate, and acetate—become bioavailable to the host. Not only are short chain fatty acids vital for the health of the lining of the gut, but they also act as mediators of inflammation in the gut and can even cross the blood-brain barrier to affect neurotransmitters in the central nervous system. Manipulating one’s diet to increase short chain fatty acids in the gut has been shown to decrease pro inflammatory markers, affect gut motility, and increase serotonin levels, reminding us that interaction of the gut microbiome and the food one eats influences nearly every aspect of one’s health.

Autism and the Dysfunctional Gut

While many medical professionals agree that there is a correlation between autism and gastrointestinal dysfunction, there are few definitive answers as to the pathophysiology behind it. However, studies that have examined the gut microbiome in individuals with autism do provide some interesting clues.

Numerous researchers have demonstrated differences in the microbiome of those with autism as compared against standard control groups. One of these studies noted significantly reduced populations of Prevotella, Coprococcus, and Veillonellaceae species, all of which ferment carbohydrates in the intestine, producing short chain fatty acids. Prevotella species functions in two important ways: it possesses the genes for the biosynthesis of vitamin B1 and high populations of Prevotella correspond to low populations of Enterobacteriaceae, such as Salmonella and Shigella, suggesting a protective effect against pathogenic bacteria. This study, in addition to finding reduced populations of fermenting bacteria, also noted that the microbiome was less populated and had a decrease in the diversity of populations of microbes in the gut of autistic individuals, with the least diversity correlating with more severe gastrointestinal problems.

With data suggesting a link between gut flora production of short chain fatty acids and gastrointestinal disturbances, some researchers have begun to explore the possibilities of manipulating the microbiome to ameliorate symptoms. For example, probiotics, like Lactobacillus, have been shown to reduce abdominal symptoms in conditions like inflammatory bowel disease and Saccharomyces is showing promise as an adjunctive treatment for diarrhea in children with autism. As scientists gain greater insight into the connection between symptoms associated with autism and the composition of their microbiome, both clinicians and caregivers may gain increased awareness of how to work with these microbes to alleviate gastrointestinal problems in the autistic patient, or perhaps even prevent them from occurring.

The Promise of New Treatments

As we continue to explore the gut microbiome, to reacquaint ourselves with this “forgotten organ,” we are finding potential new avenues of treatment for a myriad of ailments. To the millions that suffer with gastrointestinal problems, research of the microbiome has inspired several novel therapeutic strategies to alleviate their distress. For those sufferers with autism, working with the microbes in the gut may be doubly beneficial, with some data suggesting psychiatric and neurologic benefits in addition to improvement of gastrointestinal symptoms. Whether it is dietary modification, pre- and probiotic supplements, or the administration of short chain fatty acids, considering the role of the microbiome in gastrointestinal health provides clinicians with a new approach, one that works with the mutualistic interaction between microbiome and host.

The growing body of knowledge we have gained about the microbiome of the gut, even in just the last few years, has demonstrated immense potential in co-opting biochemical mechanisms, both for treating and preventing disease. Pharmaceutical companies are currently exploring bioavailable molecules that are products of bacterial fermentation in the gut as the basis for new and safer drugs. Better comprehension of the role the microbiome plays in early development may inspire methods of supporting these organisms in children as a preventive measure against future developmental dysfunction. For those already living with autism, the medical community is actively investigating these microorganisms and their role as mediators of health and disease, and each new discovery guides refinements to their methods.

As our understanding of the gut microbiome grows and informs the development of more advanced therapeutics, the future of medicine may open innumerable possibilities for potential treatments.

Foundational Medicine Review is devoted to sharing the latest research and news related to complementary treatments for autism as well as additional gastrointestinal disorders. Join our mailing list for monthly updates.

Works Cited

Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, et al. 2011. Enterotypes of the human gut microbiome. Nature. 473:174–180. https://www.nature.com/articles/nature09944

Chatterjee S, Datta S, Sharma S, Tiwari S, Gupta DK. 2017. Health and environmental application of gut microbiome: a review. Ecological Chemistry and Engineering. 24(3):467-482. https://doi.org/10.1515/eces-2017-0032

Ghaisas S, Maher J, Kanthasamy A. 2016. Gut microbiome in health and disease: linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacology & Therapeutics. 158:52-62. http://www.sciencedirect.com/science/article/pii/S0163725815002259?via%3Dihub

Guandalini S. 2014. Are probiotics or prebiotics useful in pediatric irritable bowel syndrome or inflammatory bowel disease? Frontiers in Medicine. 1:23. https://dx.doi.org/10.3389%2Ffmed.2014.00023

Hsiao EY, McBride SW, Hsien W, Sharon G, Hyde ER, et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155(7):1451-1463. http://dx.doi.org/10.1016/j.cell.2013.11.024

Kang DW, Park JG, Ilhan ZE, Wallstrom G, LaBaer J, et al. 2013. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS ONE. 8(7):e68322. https://doi.org/10.1371/journal.pone.0068322

Li Q, Zhou JM. 2016. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience. 324:131-139. https://doi.org/10.1016/j.neuroscience.2016.03.013

Linday L. 2001. Saccharomyces boulardii: potential adjunctive treatment for children with autism and diarrhea. Journal of Child Neurology. 16(5):387. https://www.scopus.com/record/display.uri?eid=2-s2.0-0034970062&origin=inward&txGid=21856636f52820f272df6e07950d679c

MacFabe D. 2015. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implication in autism spectrum disorders. Microbial Ecology in Health and Disease. 26:28177. http://dx.doi.org/10.3402/mehd.v26.28177

McElhanon BO, McCracken C, Karpen S, Sharp, WG. 2014. Gastointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014; 133(5): 872-883. https://doi.org/10.1542/peds.2013-3995

Sampson TR, Mazmanian SK. 2015, Control of brain development, function, and behavior by the microbiome. Cell Host & Microbe. 17(5):565-576. http://dx.doi.org/10.1016/j.chom.2015.04.011

Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, et al. 2017. Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine. 15:73. https://doi.org/10.1186/s12967-017-1175-y

Wasilewska J, Klukowski M. 2015. Gastrointestinal symptoms and autism spectrum disorder: links and risks – a possible new overlap syndrome. Pediatric Health, Medicine and Therapeutics. 2015(6):153-166. http://dx.doi.org/10.2147/PHMT.S85717

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