Treating autism spectrum disorder (ASD) is a challenging prospect owing to the disease’s diverse symptoms, uncertain causes, and disabling effects. Patients with autism are commonly affected by a broad array of sensory issues, sociobehavioral difficulties, and gastrointestinal malfunction, all of which can severely diminish quality of life. While some therapies are helpful, patients often still struggle to reach neurotypical levels of daily functioning. Unfortunately, the lack of curative therapies for autism often drives caregivers and patients to experiment with a plethora of ambiguously effective treatments which purport to address the disorder’s symptoms. For a growing number of families, one of those treatments is probiotics.
Probiotics are living bacterial cultures which are intended for oral consumption to confer a number of health benefits. Historically, probiotics have been attributed for long lifespans and good health in certain rural communities with diets that emphasize pickled foods; pickled foods like sauerkraut and kimchi are rich in the same beneficial microbiota which modern probiotic supplements are made from. In modern times, probiotics have been investigated as an autism-targeted therapy which could address behavioral and gastrointestinal symptoms by altering the gut microbiome. The rationale behind using probiotics to treat autism is that rectifying deviances in the microbiomes of patients with autism may help to reduce complex symptoms via the gut-brain axis. It is unknown whether this rationale is clinically sound, but it is rapidly gaining popularity within the scientific community, and researchers are currently working to gain greater clarity into the potential of gut microbiome manipulation.
At present, the Food and Drug Administration has not approved any probiotic supplement to treat any disease. Nonetheless, many patients with autism use probiotics due to their purported benefits. To determine if this is the most appropriate treatment method, it’s critical for caregivers and patients to understand the potential side effects of probiotics and consider whether there may be superior alternatives.
Probiotics Rarely Cause Discomfort to PatientsRecent reviews of probiotic side effects have concluded that most patients with or without ASD tolerate probiotics extremely well. Mild and transient gastrointestinal disturbances like nausea, bloating, gas, or diarrhea may occur, but are uncommon and appear to be innocuous. Likewise, these side effects typically are not persistent even if a patient experiences them at some point. In patients with autism, however, there may be a higher chance of experiencing these side effects. Patients with autism tend to experience gastrointestinal abnormalities at a higher rate than other people because of genetic and microbiotal factors, so caution is warranted before starting a probiotic therapy course which could aggravate an aggrieved stomach.
According to some reports, there may also be behavioral consequences to probiotic therapy. Anecdotal evidence suggests that patients with autism may be at a risk of experiencing insomnia and aggression as a result of probiotic supplementation. Likewise, sparse and anecdotal reports document behavioral regression after supplementation with probiotics. These behavioral side effects appear to be rare, and the gastrointestinal side effects tend to recede with repeated exposure. Gradually phasing in increasing quantities of probiotics may also help to avoid side effects.
Due to the mild nature of scientifically confirmed side effects of probiotics, many experiment with probiotics on their own without fear. Indeed, in the overwhelming majority of cases, the biggest risk involved in using probiotic supplements is that they might not taste very good. To solve this, commercial probiotic products can be easily mixed into other foods or administered as a flavored liquid formulation, making probiotic use more appealing. In the event of food refusal, there are also several probiotics which may be administered enterally, although it is not the preferred route.
Severe Side Effects Are Rare but Possible
The vast majority of patients do not experience any side effects from using probiotics whether or not they have ASD. There are, however, conditions under which consuming probiotics can have serious side effects. People who are immunocompromised, catheterized, or recovering from invasive surgery, for example, may want to avoid probiotics. The side effects of consuming probiotics for these individuals range from extreme inflammatory reactions to sepsis, both of which are often life-threatening conditions.
There is some evidence to suggest that patients in a heavily compromised state may be at risk of developing complications if they consume probiotics. One study, for example, found that patients who were administered probiotics while experiencing acute pancreatitis were 10% more likely to die than those who were administered a placebo. However, this study had no reference to the mechanism by which probiotics may have caused the increased mortality. Additionally, the evidence regarding probiotic side effects in severe cases is somewhat ambiguous; several pieces of literature claim that probiotics were associated with improved outcomes in the immunocompromised or recovering patient populations, whereas several others documented the negative side effects. The medical consensus on administering probiotics to these weakened patients is still forming, and firm conclusions are impossible to make. As such, patients and practitioners may want to proceed with caution. In the case of catheterized patients, probiotics may increase the risk of infection and other invasive medical devices like insulin pumps and colostomy bags likely carry the same risks. Out of an abundance of caution, patients in these conditions may want to avoid taking probiotics.
There is no evidence to suggest that patients with autism are at a higher or lower risk of experiencing these negative side effects than other patients either while healthy or while in a weakened state. However, patients with ASD who are taking probiotics may wish to reconsider their probiotic use should they fall into one of the potential risk groups above.
Unknown Side Effects And Unknown Benefits of Probiotics May Exist
As discussed, the typical side effect profile of probiotics is very mild, and the more serious side effects appear to be confined to very narrow niches, suggesting that probiotics are generally safe and well-tolerated. But it is important to realize that a comprehensive scientific account of probiotic side effects remains elusive. Several side effects of probiotics are theorized to exist but are not yet confirmed, including runaway immune activation, maladaptive bacterial gene transfer, and lactic acidosis. The implications of these phenomena vary widely; runaway immune activation could potentially be fatal, whereas lactic acidosis would merely be uncomfortable. However, as patients with autism tend to have sensory integration issues which make certain stimuli extremely unpleasant, lactic acidosis may have a particularly significant impact on these patients. Meanwhile, researchers have little understanding of what problems patients would face in the event of widespread maladaptive bacterial gene transfer, given that no mechanism has been proposed nor instances of it observed.
It’s valuable to remember that even if these side effects are confirmed to occur in certain conditions, probiotic supplementation would still remain very safe for the vast majority of patients. At present, there is no evidence to suggest that runaway immune activation or bacterial gene transfer has genuinely occurred in any patient consuming probiotics. There are, however, a small handful of reports on individual patients with short bowel syndrome who have experienced lactic acidosis as a result of their probiotic consumption. The patients experienced an array of neurological symptoms ranging from agitation to confusion, but all improved immediately upon cessation of the probiotics. These results will need to be validated in larger clinical trials before any clinical advisories against using probiotics can be made with confidence. Other therapeutics with a similar level of evidentiary backing may be more suitable for patients in the meantime.
Butyric Acid as an Alternative to ProbioticsButyric acid is a chemical produced by the gut which is responsible for regulating the gastrointestinal tract and the immune system, which may have significant implications for behavioral health due to the activities of the gut-brain axis. Notably, this critical chemical has been shown to be deficient in patients with autism, potentially contributing to ASD presentation, including the nature and severity of both gastrointestinal and behavioral symptoms. By restoring healthy levels of butyric acid and supporting the health of the gut microbiome via oral supplementation, it may be possible to disrupt these symptoms and enhance overall quality of life for patients with ASD.
Unlike probiotics, butyric acid’s side effect profile has not been linked to an increased risk of infection or serious complications in immunocompromised individuals. Patients with abnormal intestinal lengths should consult with their doctors before trying butyric acid, however. For most patients, supplementation with butyric acid is likely to have fewer and milder side effects than probiotics while delivering comparable or superior benefits via the gut-brain axis.
This picture may change depending on the latest research in probiotics, however; a large clinical trial investigating probiotic therapies for autism is underway and should be completed in November of 2018. The results of this study will be among the most detailed yet published and will describe the physiological and behavioral changes caused by several popular probiotic supplements. Any side effects will be documented alongside the physiological states which the probiotics caused to generate those effects. Caregivers may want to follow up on the trial to see whether probiotic supplementation is definitively linked to side effects that are specific to its use in patients with autism.
In the meantime, patients, caregivers, and practitioners evaluating probiotics or butyric should be emboldened by their benign side effect profiles and potential to improve the lives of people with autism. When integrated into a comprehensive treatment plan, these supplements could play an integral role in managing ASD symptoms, bringing relief and comfort to patients and their families.
Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, et al. 2008. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 371(9613):651-659. https://www.ncbi.nlm.nih.gov/pubmed/18279948/
Doron S and Snydman D. 2015. Risk and safety of probiotics. Clin Infect Dis. 60 (Suppl 2). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490230/
Hsiao E, McBride S, Hsien S, Sharon G, Hyde ER, et al. 2014. The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell. 155(7). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897394/
Munakata S, Arakawa C, Kohira R, Fujita Y, Fuchigami T, et al. 2010. A case of D-lactic acid encephalopathy associated with use of probiotics. Brain Dev. 32(8):691-4. https://www.ncbi.nlm.nih.gov/pubmed/19917522
Santocchi E and Guiducci L. 2015; ongoing. Gut to brain interaction in autism. Role of probiotics on clinical, biochemical and neurophysiological parameters. Sponsored by IRCCS Fondazione Stella Maris. https://clinicaltrials.gov/ct2/show/NCT02708901
Singhi S and Kumar S. 2016. Probiotics in critically ill children. F1000Res. 2016(5). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813632/