Learning to love our bugs

By Jerry Grillo | Emory Medicine | Oct. 26, 2016

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Illustration by Giulia Ghigini

Each of us is a mobile ecosystem teeming with trillions of living organisms.

They live on us and inside us, surround us like an invisible cloud, maintain and sustain us, ignore us, occasionally attack and kill us, and, ultimately, define us.

The human microbiome is made up of bacteria, fungi, viruses, and the like, and they cover every surface of our bodies.

"These microbiota are mostly in your gut, but also in your mouth, on your skin, in your lungs," says Emory biologist Nicole Gerardo. "They're playing critical roles in how you interact with the environment, how you process food, how you fight off pathogens, how you interact with drugs.

"Some of our remarkably fertile microbes are identical to those that live in other humans. But many are a distinct reflection of our individual experiences, shaped by who or what we've touched, where we've been, what we've breathed, and what we've consumed.

"Research interest in the human microbiome is exploding now," says Gerardo, who gave the introductory presentation at Emory's first microbiome symposium last November.

Spurred on by ambitious efforts like the National Institutes of Health's Human Microbiome Project, such research is demystifying the role of our myriad microbial passengers.

"It's like we're entering a new frontier of science, something that was basically ignored by medicine for a long time," says infectious disease researcher David Weiss, director of Emory's Antibiotic Resistance Center. "We're really at the beginning of studying all this, but I do think that in our lifetime, we'll be able to monitor each person's microbiome and intervene to improve their health. Looking at what type of bacteria we have and how resistant or sensitive they are to drugs will be an important part of health care. Most of the bugs we tote around are helpful, but they can also be ticking time bombs."

"In this case, we may be able to someday diffuse the situation, replacing pathogenic microbes with a friendlier variety."There's great promise in manipulating the microbiome, in actually changing it," says geneticist Michael Zwick. "Actually, it's already happening."

You do what?

Colleen Kraft (left) and Tanvi Dhere (right) of Emory's Microbiota Restoration Program

Colleen Kraft (left) and Tanvi Dhere (right) of Emory's Microbiota Restoration Program lead a team that has performed more than 230 fecal transplants.

Pathologist Colleen Kraft has grown used to the responses she gets in social gatherings when she brings up her work with fecal transplantation, in which gut microbes are transferred from one person to another.

 "It's been a great conversation starter at parties when people ask me what I do or what my research interests are," says Kraft, an infectious disease physician who launched Emory's fecal transplant program in 2012. "But I don't get as much laughter or as many funny looks now as I did back then."

A growing awareness of the microbiome's influence is reflected in record sales for probiotics—friendly bacteria used as a form of preventive medicine that now show up in everything from yogurt to over-the-counter supplements.

While probiotics can be used by healthy folks to restore good bacteria after a bout of antibiotics, patients who develop the potentially fatal bowel infection Clostridium difficile (C. diff) may require a fecal microbiota transplant.

Kraft and gastroenterologist Tanvi Dhere are co-directors of Emory's Microbiota Restoration Program. They lead a team that has performed more than 230 fecal transplants with an overall success rate of 98 percent.

Kraft recruits donors and maintains a stool bank, while Dhere performs and manages fecal transplant procedures.

A small fecal sample is taken from a healthy donor, processed in a lab, and transplanted into the patient's colon, where the new, healthy bacteria can restore microbiotic balance to a compromised digestive system.

"Your gut gets disrupted and barren from antibiotic use," says Kraft, the granddaughter of two farm families. "So I think of a garden analogy, or a pasture that gets decimated in winter. When our gut is decimated, using more antibiotics to treat the bad bacteria doesn't work."

A fecal transplant remains the gold standard when it comes to treating C. diff, which affects more than 450,000 people every year, killing about 29,000.

"A lot of my friends take probiotics, but that's not as efficacious as poop, which is hundreds of thousands of times more effective than typical probiotics," Kraft says. "Poop is the ultimate probiotic."

Microbes run amok

About 1,000 species of microorganisms jockey for position in our gut at any one time. Mostly, they're cooperative and helpful bugs, protecting us from pathogens with their sheer mass—there's hardly room for anything else in such a crowded community.

They boost our immune system, help keep us fit and slim, and typically exert their microbial beneficence throughout the body.

Sometimes, however, a normally harmless microbe can run amok if your system gets thrown out of whack by, say, an antibiotic or steroid. That's what happened to Gail Swanson.

About a week after returning home to Atlanta following a mission trip to Peru in June 2014, and following two trips to the emergency room with what initially was diagnosed as renal failure, Swanson was told she had C. diff. She was prescribed antibiotics and the infection subsided for a while and then returned—the beginning of a wretched cycle in Swanson's life.

"I was as sick as could be and thought, 'What hope do I have?' It felt like I was going to be like this for the rest of my life, weak and tired," says Swanson.

Her gastroenterologist told her the infection would probably go away on its own. And it seemed to, after four months of struggle.

But last summer, following a course of antibiotics to treat a sinus infection, C. diffreturned. Her physician, as many do, prescribed more antibiotics, "and I wound up in the ER with C. diff yet again," she says. "That's when I decided that I had to find another option."

A Google search led her to information about fecal transplants. "I thought, 'Yuck,' but I was desperate," Swanson says.

She was enrolled in a clinical trial at Emory testing an alternative to traditional fecal transplants—a "poop pill" designed to tease out the specific bacterial spores involved in treating C. diff. Initially, she was placed in the control group, which received the standard treatment, a powerful and expensive antibiotic called vancomycin.

"It did make me feel almost human again," says Swanson, who has four daughters and four grandchildren.

But the C. diff came back, which was expected. Finally, Swanson was given the real stuff. She calls it, "a miracle. Within two days, the C. diff was gone, and I was dancing in the streets."

"The thing of it is," she says, "I've always suffered a little bit from depression, but I must have gotten somebody's happy poop. My whole life is different."

Despite the fact that a fecal transplant is often so successful, current FDA guidelines require that a patient have several occurrences of C. diff before they can receive such a transplant, leaving doctors without many good treatment options.

"To me, it seems a little bit crazy," says Dhere. "Why subject a patient to that much infectious burden if you already know the chance of a reoccurrence is pretty high?"

So Kraft, Dhere, and others are exploring how to extend use of fecal transplants for other patients, using the therapy before C. diff takes its toll.

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