The microbiome has become one of the hottest buzzwords in science. And specifically, the gut microbiome—the delicate colony of microbes camped out in your digestive tract—has attracted intense attention from scientists and quacks alike.
Our abundant microbial inhabitants have been theorized to influence our mind and behavior, and may play a role in conditions such as Parkinson’s disease and depression. But some advocates have put the cart before the horse, and pushed the theory to link the microbiome to nearly every illness or condition. And a condition as poorly understood as autism presents a particular inviting area for probing.
We don’t yet know the root cause of autism, though genetic factors are thought to be involved. But some research has hinted that the gut plays a role. Much of the evidence to support the theory has come from studies in animals; for example, when scientists put fecal samples from children with autism into mice, colonizing their stomachs with their microbes, the animals developed autism-like behaviors. These studies were thought to suggest a causal relationship between gut bacteria and the development of autism—but rodents are a poor proxy for the complexities of autism and the human mind. Other studies have found that children with autism tend to have a different microbiome makeup compared to children not on the spectrum. But it’s never been clear whether this divergence in gut flora is a cause or an effect. Now, a new paper in the journal Cell argues for the latter: The difference stems from the kids’ eating behaviors, and may be a consequence, not the cause, of their symptoms.
A team of researchers at the University of Queensland, Australia, looked at the stool samples of almost 250 children, of which 99 were diagnosed with autism. These participants had previously also provided clinical and biological data to the Australian Autism Biobank and the Queensland Twin Adolescent Brain Project. Using this data, and comparing it to the stool samples, the researchers found that an autism diagnosis was associated with a restricted and poor diet, as autistic people tend to have a keener sensitivity to—and dislike of—certain foods. (Children with autism have a higher tendency to suffer from gut-related issues, such as constipation, diarrhea, and stomach pains; the share who suffer from gastrointestinal issues is estimated to be as high as 70 percent.) This in turn was linked with lower microbial diversity, suggesting that autism-linked behaviors may explain away the differences in microbiome makeup, rather than the other way around.
The researchers looked at over 600 species of bacteria identified in the gut microbiomes of the study’s subjects, and found only one—Romboutsia timonensis—to be associated with an autism diagnosis; the species was significantly less abundant in the autistic participants. The two datasets allowed them to look closer at the participants’ diets, and they found that those of autistic people were significantly less diverse and of lower quality. When they looked at the participants’ DNA, they found a correlation between genetic indicators linked with a higher risk of autism and that person having a less diverse diet, but not a direct correlation between autism risk and the inhabitants of the person’s microbiome. Their results, says lead author Chloe Yap, suggest that it’s the very traits of autism that contribute to these microbiome differences. “That was the most surprising thing to me,” she says. “That it is just so simple.”
The study “validates a lot of what people have been thinking,” says Calliope Holingue, a psychiatric epidemiologist at the Center for Autism and Related Disorders at Kennedy Krieger Institute in Maryland, on whether the connection between autism and the microbiome may be partially due to diet. “That being said, I think it doesn't totally erase the possibility that the microbiome does play a role in autism itself.”
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One critique, she says, is that the study looked at a snapshot in time, rather than over a long period. “Even though the authors didn't find that autism itself was associated with gut microbiome composition or diversity, that doesn't mean that the microbiome wasn't involved at some point, prior to the study, for example,” says Holingue. Yap acknowledges that in order to assess causality, longitudinal studies will be important.
While no study so far has conclusively shown it, the early hints at a relationship between the gut and autism seeded hopes for a treatment. For example, a research group at Arizona State University published a study in 2017 that took 18 children on the autism spectrum who also suffered from gastrointestinal problems, and administered them with a fecal transplant. In 2019, the team published a two-year follow-up, and reported a nearly 50 percent improvement in autism-related symptoms. But the study wasn’t randomized, didn’t have a control group, wasn’t compared to a placebo, and had a small sample size.
The Arizona State University studies have been a source of controversy within the field, says Holingue. “Some people are big fans of them. And I think some of the other people are very concerned that they do more harm than good, and maybe are unclear what the aim is,” she says. A real source of contention among autistic people and their families has been whether the ultimate goal of research should be to search for treatments. “A lot of the autistic community has been pretty vocal about saying that they don't want research to focus on cures for autism or treatments for autism, but rather co-occurring conditions and things that support them,” Holingue says.
Despite the lack of concrete evidence to support efficacy, the early research has encouraged clinics to offer treatments for autistic people, including interventions such as probiotics, prebiotics, and fecal microbiota transplants, or FMTs (or, less often, “transpoosions”). Fecal transplants—in which the microbes from the poop of a healthy person is administered to the patient either anally or orally—have been shown to benefit some conditions: specifically, in treating Clostridioides difficile colitis, an often debilitating, sometimes fatal, condition which arises from the overuse of antibiotics, obliterating bacterial balance in the gut. This success has mutated into hype over trying the treatment out on more and more conditions—autism included.
“When autistic people or [their] families receive the news that someone is autistic, they are just left with zero effective support,” says James Cusack, the CEO of Autistica, an autism research charity in the UK, who is on the spectrum. “And that can be a very traumatic experience for families and for autistic people.” It also means that a parent could feel forced to find alternative ways of ensuring that their child thrives in the same way as their peers. (One 2015 study surveyed parents and found that nearly nine in 10 had sought out complementary and alternative medicine for their children’s autism.) These parents might be more susceptible to trying out things which are really not evidence-based at all, Cusack says. “And it's really sad that people are in this position. What we should be trying to do is to try and understand the reasons people make these decisions and try to support them to take a different approach.”
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“I think for most traits or conditions, there wouldn't have been as much excitement or hype around this—tenuous, essentially—link at this point,” agrees Yap. “But I suppose the key difference with autism is that there's so much that we don't know. That's really challenging for parents, because they really just want to do the best for their child.”
Yet speculative treatments can be vastly expensive and, given the dearth of evidence to bolster their efficacy, potentially harmful. Fecal transplants in particular are still considered experimental, and are by no means risk-free: In June 2019, the US Food and Drug Administration announced that two people who had received fecal transplants had developed multi-drug-resistant infections from bacteria in the stool, and one died. Both were participating in clinical trials of these transplants, one investigating their effect before a stem cell transplant and the other as a treatment for hepatic encephalopathy, a brain disorder triggered by severe liver disease.
Providing these transplants to kids with autism is a nascent industry. Novel Biome, a Canadian company that offers fecal transplants for the treatment of children with autism, has centers in Mexico, Hungary, and Australia, with more coming soon, according to the company’s website. The total cost of a full treatment course comes out to a hefty $14,300. Yet in late August, the College of Naturopathic Physicians of British Columbia announced it was investigating the company after a whistleblower alleged that the founder, Jason Klop, was manufacturing these products in a “household lab” without standard procedures or quality control—including that he had used the stool of his nephews. In response, Klop filed a petition in the Supreme Court of British Columbia in November asking for the investigation to be quashed, on the basis that it was "unscientific prejudice" against fecal transplants. Health Canada, the nation’s federal health body, has initiated an investigation into Klop's operation and instructed him not to accept Canadian children on his retreats.
The new University of Queensland study offers a pessimistic prognosis for the theory that poop transplants or other gut-based interventions can help autistic people. If the lack of microbiome diversity is a symptom, not a cause, there’s not much they can do to address autism’s roots. But Yap feels her study offers insights into other things parents can do to help their children. “Our results highlight the importance of a healthy, balanced diet for kids on the spectrum, and a critical need to support children and families at mealtimes, and research into how to best support families and children to eat well,” she says.
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