Could the Microbiome Cure Eating Disorders?

To someone who was starving, the hospital tray full of food probably looked like a feast. But to me, the tray—with a rapidly cooling slice of pizza, side salad, carton of milk, and some sort of pudding thing for dessert—represented everything I feared. I had been hospitalized for anorexia, and the only medicine for my shriveled heart muscle and shutting down organs was food. I had to eat.

Eating, however, was the most terrifying thing anyone could have asked me to do. If the ninth-floor hospital windows would have opened, I would have been less scared about jumping than about taking a bite of pizza. I was terrified of weight gain, terrified of anything that would shatter the iron grip I (thought) I had on my eating and my life.

There was another reason I avoided eating: It was really uncomfortable. I’m not talking psychic discomfort, although that was plenty real. I’m talking severe bloating, constipation (there’s a reason everyone on eating disorder units talks about pooping), gas, cramping, and never-ending stomachaches. I had been hospitalized before, and as much as knowing the drill gave me some small amount of comfort, I also knew what was coming. Learning that I was right gave me little comfort.

My psychiatrist calmly explained why the process was so miserable for me. Deprived of food for so long, my digestive system started to atrophy. In some sense, it forgot how to process food. My stomach had shrunk, which made me feel full on a tiny amount of calories. All of these were technically correct, but what neither of us knew almost 15 years ago was that another factor could have been at play.

Our guts are home to trillions of microbes that help us digest our food and keep harmful pathogens from taking over. A host of studies in recent years have shown that changes in diet rapidly shift the populations of microbes living in our guts, and eating disorders, according to a recent study in the International Journal of Eating Disorders, are likely no different. Knowing that there’s a difference is one thing, but knowing what that difference means is quite another.

“So far, we have focused on gut-related disorders such as C.diff infections and Inflammatory Bowel Disease, but we wanted to find out if perhaps this largely psychological disease had any microbial signature. Today there are roughly 30 million individuals suffering from anorexia, bulimia, and binge eating disorder, yet, research in this area beyond psychological intervention and treatments is largely unexplored. We want to see how these diseases might be impacting the gut or vice versa,” said Orli Kadoch, Research and Collaborations Lead at uBiome, in an email.

Deprived of food for so long, my digestive system started to atrophy. In some sense, it forgot how to process food.

UNC eating disorders researcher Cynthia Bulik is spearheading two different studies looking at the microbiome in eating disorders. One of them, funded by the National Institute of Mental Health, will track the microbiomes of 100 people with anorexia from the time they’re first admitted to the hospital until they are discharged at a healthier weight, and even beyond. The other study has paired with biotech startup uBiome to gather microbiome samples from people with anorexia, bulimia, and binge eating disorder from around the U.S. to gain a more comprehensive picture of eating disorders and the microbiome. Bulik and other eating disorder experts hope that these studies will help tease apart the biology of eating disorders and provide new insights into treatment.

Part of the problem with explaining the biology of eating disorders to people, Bulik says, is that we really don’t know very much. We know, for example, that eating disorders are the most lethal of all psychiatric illnesses, but we don’t really know why a small subset of the population can essentially starve itself to death while so many others struggle to lose even five pounds, or why other people can repeatedly overeat far past the point of fullness. No one really expects a simple answer to these complex disorders, but the microbiome is an important area that hasn’t yet been explored, says UNC microbiologist Ian Carroll and a co-investigator on the NIMH study.

“That the microbiome of anorexia nervosa hadn’t been studied was mind-boggling,” Carroll says.

Although the popular saying says that the way to your heart is through your stomach, emerging research shows it’s also the way to your brain. Scientists call it the gut-brain axis, and it’s clear that the microbes in the gut can have an effect on the brain. One study found that mice raised in a germ-free environment, and therefore without a microbiome, showed significantly less anxious behavior than their germy counterparts. A more recent study found that a daily probiotic supplement significantly decreased anxiety in humans.

Studies have also shown, for example, that gut microbes can affect weight gain. Fecal transplants from obese to lean mice caused the more svelte rodents to gain weight, and vice versa. And scientists have documented a case report of a woman who started gaining large amounts of weight after receiving a fecal transplant from her larger-bodied daughter.

A pilot study of microbiomes in people hospitalized for anorexia revealed marked differences between admission and partial weight restoration. At their lowest weight, the study participants had gut microbes that were significantly less diverse than at a more normalized weight. The reason, explains Bulik, is that the extremely low-calorie diets of those with anorexia create a harsh environment where it’s tough for even gut microbes to get enough energy. The few species that can survive are those that can eke out a living on very few calories.

“It practically defies the laws of physics how some of these people can live on so little for such a long period of time and still be alive,” she says.

That changes during refeeding, when high-calorie hospital diets provide many more nutrients, which allows for a more diverse microbiome.

“And a diverse microbiome is a healthy microbiome,” Bulik says.

“That the microbiome of anorexia nervosa hadn’t been studied was mind-boggling.”

The high calorie refeeding diet also has a paradoxical effect on many people with anorexia, causing their metabolisms to become extremely inefficient, such that calorie needs go even higher. Many with anorexia need upwards of 3,500 to 4,000 calories per day to gain a pound a week. No one really knows why this is, but Bulik and Carroll intend to investigate their microbial samples to see whether particular microbial species might play a role in this.

Bulik and her team have continued following the study participants after discharge. Generally, Bulik says, about half of the people who are hospitalized maintain their gains while the other half tends to relapse. She is investigating whether the gut microbiome plays a role in determining whether someone relapses after treatment. It could be that certain microbial species perpetuate the hypermetabolism seen during refeeding and make it more likely that some people will lose weight after discharge. Other microbes might have stronger behavioral effects.

The new NIMH grant will also allow them to take a subset of the microbial samples and transplant them into mice.

“We will be taking the microbes out of a complex environment and placing them into a much more controlled one to study their functional impact on weight and behavior,” Carroll says.

Initially, this study was as far as Bulik had thought about microbiome studies for the time being. But as she scrolled through Facebook several months ago, she saw an ad for uBiome and decided to give them a call, and the partnership blossomed from there.

“We will be able to reach so many people this way that we wouldn’t be able to through traditional study methods. It’s delightfully exciting,” Bulik says.

The new partnership with uBiome opens the door to understanding a broader range of eating disorders across a broader population. What little work that has been done on eating disorders and the microbiome has focused on anorexia, and there’s good reason to believe that other disorders also affect—and are affected by—the trillions of microbes living on the body. The uBiome study is open to pretty much anyone in the world.

Interested participants can go to the uBiome website, where they will fill out a brief screening questionnaire. If they fulfill enough of the study criteria, uBiome will mail them a kit that they will send back with a stool sample inside (yes, you’re collecting bits of your own poo. But, you know, for science!). The folks at uBiome will conduct the microbiome sequencing, while UNC will handle the data analysis. Participants will also fill out a more detailed, study-specific questionnaire.

So far, Bulik says, everyone has been enthusiastic about participating. “No one has turned us down. It’s much easier to get people to donate poo—something you normally flush down the toilet—than to donate blood,” she said.

“This crowd-sourced eating disorder study is the first of its kind and we couldn't be happier to partner with such an innovative team at UNC.  We hope this research will spark more efforts and hopefully do a lot of good for this community,” Kadoch says.

It’s unlikely that these studies will tell us everything we need to know about the microbiome as it relates to eating disorders, but it’s a start. And beyond understanding the biology of eating disorders, this microbiome research may do something more immediate and practical for sufferers: make the process of renourishment less painful.

“No one really knows what makes refeeding so uncomfortable. Maybe we can harness the bugs through a targeted probiotic supplement to make the process easier to people can focus more on getting well,” Bulik says.