Michael, an autistic boy living in New York City, started scratching and picking at his face when he was about seven years old. Before long, he was gnawing on the side of his thumb. Along the bottom of his stomach, he tore cuts so deep that they scarred.

Over the next five years, a series of psychiatrists prescribed psychotropic medications to correct the self-mutilation. But nothing seemed to help. By age 12, he'd been taken out of school because he was a constant disruption. Though his parents wanted him to live at home, they decided he could be better cared for in a residential facility.

As they prepared to move Michael to the group home, his family was referred to Dr. Kara Margolis. Margolis, 36, is a pediatric gastroenterologist at New York Presbyterian Hospital and a researcher at Columbia University Medical Center. She speaks with contagious enthusiasm and the slightest hint of a Brooklyn accent. By the time she met Michael, bloody scabs dotted his face, from the tender skin below his eyes to the tips of his ears. He'd chewed his thumb down nearly to the bone. There was blood everywhere, Margolis recalls as she describes their first visit. He screamed and paced the room throughout the brief exam.

Until recently, psychiatrists have mainly been handling these kinds of behavioral changes. "A lot of these kids, before they see me, have been trialed on many different psychotropic drugs to try to relax them, to calm them down," Margolis explained on a Wednesday morning in April, as she sat at her cluttered desk in the gastroenterology research lab at Columbia. "Sometimes they work and sometimes they don't."

Dr. Kent Williams, a pediatric gastroenterologist at Nationwide Children's Hospital in Columbus, Ohio, agrees that many doctors are reluctant to consider other possibilities. "My heart goes out to the parents, because this is a daily struggle," he said. "Some physicians don't know what to do, so they give up."

Margolis, Williams and a handful of doctors across the country take a different approach. Instead of concentrating on the brain, they treat the gut.

Dr. Kara Margolis examines a patient. [Danielle Elliot]

"Many doctors don't recognize that aggressive behavior is not part of autism," Margolis said. "This is really a new field." Research is showing that a common cause of autistic children acting out is simply because they're constipated -- which, from there, can mean they stop sleeping and eating well. They may become aggressive and frustrated because they have no other way of saying that their stomachs hurt.

Approximately one in 88 children in the U.S. has an autistic spectrum disorder. Up to 70 percent of them have gastrointestinal (GI) abnormalities at some point during childhood or adolescence. They are 3.5 times more likely to have constipation or chronic diarrhea than children who are not autistic. For years, parents have tried altering their children's diets to alleviate the issues, often restricting or completely eliminating gluten and dairy. But there is little scientific evidence supporting these dietary changes. Still signs keep pointing back to an underlying biological link between autism and GI issues.

A study published last year in the Journal of Abnormal Child Psychology linked the GI issues with behavior, showing that autistic children who have GI issues often experience extreme anxiety as well as regressions in behavior and communication skills. What's worse, the side effects of the psychotropic drugs that are prescribed to many autistic children may be intensifying the digestive issues. Once the GI issues are treated, aggressive and problematic behaviors sometimes subside.

At her first visit with Michael, Margolis suspected that he was nauseous and constipated, conditions that generally manifest in the area of the stomach where he was scratching. The nausea would explain why he often gagged and salivated during meals. She couldn't take x-rays because he was so hyperactive, but Margolis followed her instincts and treated him for constipation and reflux (gastritis).

When Michael came in for his follow-up one month later, the scabs on his face were healing. He'd stopped biting and scratching; he sat through the exam. His mother cried in the exam room, seemingly amazed that over the five years that his behavior deteriorated, no other doctors had recognized the GI issues.

Today, he is back in school and living with his family. He is still very sensitive to the slightest bit of constipation, but as long as his GI issues remain in control, so do his behaviors.

"These are kids who, their whole lives turned around when we treated the GI issues," Margolis said. "They're not miracles. They seem like miracles, but really all it takes is a recognition that GI things happen in these kids and they manifest in very different ways than in kids who are not autistic." Understanding how GI issues manifest differently in autistic children could lead to new treatments and pharmaceuticals targeted specifically to the autistic community.

Dr. Kara Margolis consults with a patient's mother. [Danielle Elliot]

There are several theories behind the link between GI issues and autism, and whether abnormal gut development precedes or contributes to abnormal neurological development. There is no evidence to say that GI issues and autism have a causal relationship in either direction. The first step to improving treatments is to understand the underlying link between the two conditions.

Scientists at U.C. Davis, supported by a $770,000 grant from Autism Speaks, are concentrating on bacterial overgrowth in the gut and potential antibiotic treatments that would help the gut function more normally. At the University of Toronto, neuroscientist Derrick MacFabe is researching the relationship between gut bacteria and brain development.

Margolis is also investigating the role of gut bacterial overgrowth -- as well as that of serotonin.

Serotonin is best known for its role in the central nervous system. It regulates mood, appetite, and sleep -- yet more than 90 percent of the body's serotonin is actually in the gut. Dr. Michael Gershon, author of the The Second Brain: Your gut has a mind of its own and head of the gastroenterology lab at Columbia, was one of the first to study the role of serotonin in the gut -- or, as he calls it, the enteric nerve system. His research shows that serotonin regulates movement within the intestines, which is critical to healthy digestion.

A 2009 study found that about 30 percent of autistic children have too much serotonin. In medical terms, this is called hyperserotonemia. In the gut, serotonin is produced by two different enzymes. Once it is released, digestion kicks into action, and the serotonin needs to be reabsorbed for the gut to return to the normal resting state. Reabsorption is carried out mainly by the serotonin re-uptake transporter (SERT), which is carried in gene 17q11.2. If sufficient serotonin isn't produced, or it isn't reabsorbed, GI issues ensue.

In a 2012 study, researchers at Vanderbilt University identified the most common genetic SERT mutation (SERT Ala56) in the genomes of hyperserotonemic autistic children. After pinpointing SERT Ala56, they created autistic-like mice by manipulating their SERT. These mice exhibited communication delays and repetitive behaviors similar to those observed in children with autistic spectrum disorders. When the Columbia researchers joined the study last year, they started to investigate gut development in the SERT Ala56 mice.

"So far we found that these mice do have huge differences in the way that their guts develop," Margolis said. "They're constipated, like a large number of kids with autism; they have bacterial overgrowth in their guts, which we think also happens in a lot of kids with autism; and we'll be looking at other aspects of these mice with gut function as well."

At this stage of the study, they're looking at tissue samples to see if similar abnormalities occur in human development. If they do, it will tell the researchers one of two things: either they are right that the serotonin imbalance affects gut development, or that the serotonin imbalance is a coping mechanism for something else.

In both cases, it would mean that treatments for GI issues should be different for autistic patients than they are for non-autistic patients. "The idea would be to target treatments to figure out what's going on in the serotonin system in the gut," Margolis said. "And to be able to treat these kids more effectively based on the defect that's causing the hyperserotonemia."

Williams is also investigating the role of serotonin in GI dysfunction among autistic patients. He is in the early stages of comparing tissue and blood samples from autistic and non-autistic children with GI issues. Like Margolis, he hopes the research will lead to new treatments for autistic patients. "Do these kids respond in the same way? Do we need additional interventions?"

One of the biggest challenges is dealing with the children's sensory issues. Once autistic children start to recognize the taste or texture of medications, Williams said, many of them start refusing to take them. Margolis regularly treats a 10-year-old boy who spots the prescription pills that his mom mixes into his trail mix. He picks them out and throws them across the room. Autism-specific treatments would address these sensory issues in the medication plan.

"There's not a lot out there on how to approach and treat these kids," Williams concluded. "So, I think there's a lot to be done." He stressed that educating physicians, especially those who don't often treat autistic patients, is key to helping diagnose and mitigate GI issues.

This year Margolis is also collaborating with Drs. Harland Winter, Tim Buie of Massachusetts General, and Dr. Agnes Whitaker from Columbia on a separate study supported by the Autism Treatment Network. Through a questionnaire, they are pinpointing the most common GI problems in autistic children, as well as confirming the link between these conditions and problematic behaviors.

The preliminary results of the study support something Margolis has already seen in her clinical practice: not all autistic patients respond to GI issues aggressively, but their behaviors and reactions can be severe in other ways. If an autistic child's behavior suddenly shifts, doctors should consider GI issues as a potential cause.

Last year, Margolis treated an 8-year-old boy for constipation. Six months before coming in, the boy was developing well. He was reading, speaking, and doing math with home-school tutors. Then, after a family vacation, he became nearly catatonic and obsessive compulsive to the point of dysfunction. He drank water so excessively that his sodium dropped, causing him to have several seizures. Margolis says he was severely constipated. Once treated, he started to improve. Within months, he was back to his old self.

Margolis and Williams can share many stories like these, stories of patients whom they've seen transform once they are treated for conditions as basic as constipation and reflux.

"You would say it was a miraculous recovery," Margolis said during a rare five-minute respite between patients at New York Presbyterian. "But I think these kids just live in a very fine balance. And when anything is off, they regress, because they compensate."

"There are many other causes for these things, so I don't think that everyone that has these behaviors has a GI problem," she added. "I certainly don't solve every case. But I think for sure that a GI evaluation is warranted in the majority of these kids."