🔄FROM THE ARCHIVE: Researchers are finding clues to autistic behavior — in patients’ gut bacteria. Using fecal transplants to improve symptoms have shown promise in preliminary studies.
It’s not always easy to convince people that the human gut is a sublime and wondrous place worthy of special attention. Sarkis Mazmanian discovered that soon after arriving at Caltech for his first faculty job 14 years ago, when he explained to a local artist what he had in mind for the walls outside his new office.
Everything changed when he took his first biology class. Hunched over his new, thick textbook in the library, reading about basic biological concepts like photosynthesis, Mazmanian felt a vast new world opening up to him. When Mazmanian dug further, he found that no one had yet answered what seemed to him to be the most obvious question: Why would the human immune system, designed to attack and destroy foreign invaders, allow hundreds of species of bacteria to live and thrive in our guts unmolested? To him, the bacteria’s survival implied that we had evolved to coexist with them. And if that were so, he reasoned, there must be some benefit to both the microbes and the human body — a symbiotic relationship.
“That was exciting, right?” Mazmanian recalls. “Obviously I repeated it and tested it in a number of different ways. Then I asked the next question: ‘Can I restore the [immune] function in an adult animal?’ ” As Mazmanian tells it, Patterson was a man of few words, and at lunch Mazmanian was “going on and on” about his own work.
Throughout the winter and spring of 2012, Mazmanian and Patterson continued their conversation. Mazmanian found distinct differences in the microbiomes of the mice. And, they noticed, the mice with the features of autism had leaky gut syndrome, an increased permeability of the gut lining that can allow pathogens and allergens to leach out. This condition had also been reported in children with autism.
Krajmalnik-Brown and Adams launched a preliminary trial to test the effects of fecal transplants on 18 children between the ages of 7 and 16 with severe autism, who also had severe GI issues. The researchers administered powerful antibiotics to kill off the microbiomes of the children and followed them with a bowel cleanse. They then replaced the microbes with transplanted flora taken from the guts of healthy neurotypical adult volunteers.
In their first report on the trial in 2017, the team highlighted a number of distinct changes in the microbiome after the transplants, in particular a surge in the populations of three types of bacteria. Among them was a four-fold increase in Bifidobacterium, a probiotic organism that seems to play a key role in the maintenance of a healthy gut.
What’s more, some have speculated that the tendency of children with autism to experience sensory overstimulation may stem from the inability to tamp down overexcited neurons. A lack of GABA could lead to just that. “The paper made a big splash, but trying to model psychiatric-related human conditions in mice, in my view, is a little bit of a stretch,” says Sangram Sisodia, a neurobiologist at the University of Chicago who studies the microbiome. “A mouse with autism?”
Ethan Loyola had GI issues and symptoms of autism until researchers introduced new microbes to his gut. His mother says the treatment changed everything. Prior to his fecal transplant at age 7, Ethan Loyola suffered from chronic and severe diarrhea, constipation and cramping, symptoms so extreme that to his mother, Dana, he sounded like “a bit like a woman in labor when he was trying to have a bowel movement.
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