Autism spectrum disorder (ASD) drastically shapes the lives of patients and caregivers, often presenting innumerable challenges that greatly compromise quality of life. Despite years of research, there are presently no curative therapies nor combination of therapies that can treat the root causes of the disorder. However, there may be new hope for patients struggling with ASD. Though autism has traditionally been considered a predominantly behavioral disorder, more recent perspectives incorporate gastrointestinal dysfunction and metabolic aberrations into the disorder’s pathology. As a result of this new understanding, gastrointestinal symptoms like diarrhea and constipation join behavioral features like social withdrawal and repetitive behaviors as primary symptoms which signify the disorder. However, some researchers are going one step further: they believe that problems of the gut may play a causative role in some behavioral autism symptoms. In light of this hypothesis, new therapeutic strategies are being designed around the idea that it may be possible to alleviate ASD symptoms by rectifying patients’ GI difficulties. Now, a growing number of researchers believe that butyric acid supplementation may be a particularly promising treatment, potentially opening up the door to greater healing.
The Prevalence of GI Symptoms in Patients with Autism
Gastrointestinal difficulties and poor gut health are very common among patients with ASD. According to one 2003 study, at least 24% of patients with autism experienced chronic gastrointestinal problems, most commonly diarrhea and constipation. Chronic diarrhea was reported by 17% of patients in comparison to a statistically negligible quantity of healthy controls, suggesting that patients with autism experience excessive gut motility or an inability to successfully absorb liquid from their food. Constipation, on the other hand, would signal a deficit of gut motility. These conflicting symptoms may occur at different times in the same patient, making identification of disease pathology difficult. No matter the cause, inconsistency in the data of ASD research is common owing to the disease’s multifactorial complexity.
Some research reports suggest that the number of patients with GI issues and ASD may be even greater than 24%. A 2002 study found that 41% of patients with ASD chronically experienced an average of four or more gastrointestinal symptoms without an identifiable cause—36% more than healthy controls. In contrast to the 2003 study, the 2002 study found that generalized abdominal discomfort was the most common symptom in patients. The consequences of these gastrointestinal symptoms were often behavioral symptoms like irritability or unexplained crying, both of which chronically co-occurred in over 40% of patients with autism with GI symptoms.
But the prevalence and severity of gastrointestinal symptoms are only one part of the story; the intestines of patients with autism are dysfunctional in ways that patients may not directly feel. Significantly, the 2002 study identified that 23% of patients with autism experienced rapid cycling between symptoms of diarrhea and constipation from day to day. This would suggest that there is more than one pathology implicated in the gut symptoms of ASD. To understand what one of these pathologies might be, researchers are now examining the gut microbiome of patients with ASD.
The ASD Microbiome
The gut microbiome of patients with autism is a critical factor in their gut health and their gastrointestinal symptoms. Importantly, a growing body of research shows that the gut microbiome in patients with autism is markedly divergent from the gut microbiomes of healthy people. The microbiome under normal circumstances is populated by hundreds of different species of beneficial bacteria. These bacteria are responsible for helping with digestion and, by virtue of occupying all of the habitable areas of the gut, prevent other bacteria which may be harmful from becoming established. However, disproportionate representation of healthy bacteria may still be detrimental.
A 2002 study found that of the bacteria species common to the human microbiome, patients with autism had far greater numbers of each species than healthy people. Using stool samples, researchers found that patients with ASD had roughly 2.1 million bacteria for each of the common microbiome species in their stools while people without ASD had a mere 160,000 specimens of each species in their stools. Additionally, patients with autism experienced a proportionally larger population of bacteria within the Clostridia genus than healthy people. The study also showed that patients with ASD had strains of bacteria which are not found in healthy people. 80% of patients with autism had non-spore-forming anaerobic and microaerophilic bacteria, whereas 0% of the healthy control had similar colonies of these types. For 50% of the patients with ASD who experienced the divergent bacteria, there were upwards of 7 different species of microbiota which were not found in healthy controls. The remaining patients had fewer variant species. These discoveries provide overwhelming evidence that patients with ASD have difficulty regulating their microbiomes in the same fashion as normal people.
Troubles in the microbiome can easily throw the entire GI system out of working order. 50% of the patients had a highly acidic pH level in their stools, though the amount of acidity beyond normal ranges varied immensely from patient to patient. This acidity was likely the result of the stools being heavily laden with microbiota. An acidic pH within the gut itself could cause any number of different symptoms, including bloating and gas, and it’s likely that the magnitude of deviation dictates the magnitude of the symptoms the patient experiences. One patient’s fecal sample registered a pH of 1.8; normal ranges in the gastrointestinal tract are from 7.4 to 6.7 depending on where the sample is taken. The consequences of this difference were substantial, leading to significant gastrointestinal distress. Overall, the vast majority of patients (67%) reported more frequent episodes of diarrhea and constipation than healthy patients. Considering the extreme disparity in microbiome makeup that correlates to these symptoms, restoring the microbiome of patients might be the key to easing gastrointestinal distress.
The Frontier Of ASD Therapy: Butyric Acid
Presently, there are no FDA-approved medications designed to target the gut microbiome of patients with autism. However, new therapies isolated from chemicals produced by the body are increasingly promising avenues of research. Among these new therapies, the chemical called butyric acid has seen early successes in the laboratory. Researchers have long known that butyric acid is an intercellular signaling molecule and immunoregulator; the body produces butyric acid to use in these capacities. More recently, however, butyric acid was identified as a modulator of gene expression in ASD in a 2015 study published in Microbial Ecology in Health and Disease.
This study shed light on butyric acid’s ability to govern the behavior of cells in the gut in patients by linking the level of butyric acid to intestinal cells’ ability to produce energy. In the estimation of the study’s authors—and their peers—80% of patients with autism exhibit abnormalities in their cellular mitochondria, which produce energy for cells. These abnormalities could range from excessive throughput of energy to heavily inhibited energy production. Depending on the cell which has malfunctioning mitochondria, the resulting impact on organ tissues may vary. For white blood cells, abnormal energy production could result in an inability to ward off infections, or, alternatively, excessive inflammation. Excessive inflammation causes pain and bloating for patients while also reducing the ability of the intestines to absorb nutrients and water. More importantly, butyric acid can modulate these mitochondrial extremes and bring them toward a healthier level of activity. Thus, it may be possible to treat ASD-affiliated gut inflammation using butyric acid by virtue of its direct impact on white blood cells.
However, butyric acid can also improve the health of the gut via another mechanism: by modulating the behavior of the white blood cells in the colon, the microbiome of patients with autism is normalized with regard to the proportions of the bacterial colonies. Because the white blood cells affected by butyric acid will produce less inflammation, the normal and healthy bacterial populations of the microbiome will flourish. When the normal bacterial populations are given the conditions that are right for them to grow, they can out-compete the potentially harmful aberrant bacteria and thus promote better gut health, alleviating GI symptoms. Significantly, for some patients, the reduction of gastrointestinal symptoms may also produce meaningful emotional and behavioral changes as physical distress is lifted.
Seeking Relief Today
Microbiome medicine is a rapidly developing field, and many questions remain regarding butyric acid’s impact on the microbiome and the cells responsible for the microbiome’s cultivation. At present, researchers are clear that butyric acid induces genetic changes in colonocytes which modulate their metabolic activity, but the nature of these changes is an area of active investigation. However, the current evidence combined with the knowledge that patients with autism are typically deficient in butyric acid suggest that it may be prudent to begin butyric acid supplementation even now. While rigorous clinical trials of these supplements are still in progress, early adopters of the therapy could experience multidimensional symptom relief and, ultimately, enhanced quality of life.
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