Gulp: Adventures on the Alimentary Canal

17. The Ick Factor WE CAN CURE YOU, BUT THERE’S JUST ONE THING

IT IS A standard party invitation in most respects. There’s a street map of the neighborhood, the address and time of the party, and some friendly encouragement to bring the whole family. The decorative elements, though, are unusual: a cutaway illustration of the interior of the human colon, its parts neatly labeled. Above this, in a festive typeface, it says, “Gut Microflora Party!” The host is Alexander Khoruts, a gastroenterologist and associate professor of medicine at the University of Minnesota. Along with the usual complement of colonoscopies and dyspepsia consults, he performs transplants of colon bacteria—aka gut microflora.

Almost everyone gathered at the party this evening is involved with this work. There is Mike Sadowsky, coeditor of the textbook The Fecal Bacteria and Khoruts’s research partner. Leaning into the buffet is Matt Hamilton, a University of Minnesota postdoc student who prepares the matter for transplant. Matt is spooning Khoruts’s homemade Russian red beet salad onto a plate, enough of it that a nurse tells him he’s going to “look like a GI bleed” tomorrow.

The nurse admires a platter of chocolate-covered whole bananas, one of the thematically appropriate desserts created by Khoruts’s thirteen-year-old. James is very much his father’s son, intelligent and cultured, with a sly sense of humor. He plays classical music on the grand piano in the living room and would like to write novels one day. The nurse asks James what number the desserts[118] would be on the Bristol Stool Scale. He replies without hesitating—4 (“like a sausage or snake, smooth and soft”).

It’s tough to find an inappropriate mealtime conversation with this group—not because they’re crass or ill-mannered, but because they view the universe of the colon very differently than the rest of us do. The interactions between the human body and its gut microbiome—as our hundred trillion intestinal roomers are collectively known—is a hot research area of late. For decades, medical investigators have looked at the role of food and nutrients in disease treatment and prevention. That has begun to seem simplistic. Now the goal is to tease apart the interactions between the body, the food, and the bacteria that break down the food. One example is the cancer-fighter du jour: the polyphenol family, found in coffee, tea, fruits, and vegetables. Some of the most beneficial polyphenols aren’t absorbed in the small intestine; we depend on colonic bacteria to metabolize them. Depending on who’s living in your gut, you may or may not benefit from what you eat. Or be harmed. Charred red meat has long been called a carcinogen, but in fact it is only the raw material for making carcinogens. Without the gut bacteria that break it down, the raw goods are harmless. (This applies to drugs too; depending on the makeup of your gut flora, the efficacy of a drug may vary.) The science is new and extremely complex, but the bottom line is simple. Changing people’s bacteria is turning out to be a more effective strategy for treatment and prevention of disease than changing their diet.

As a member of a culture that demonizes bacteria in general and the germs of other people in specific, you may find it disturbing to imagine checking into a hospital to be implanted with bacteria from another person’s colon. For the patient I’ll shortly be meeting, a man invaded by Clostridium difficile, it’s a welcome event. Infection with chronic C. diff—to use the medical nickname—can be an incapacitating and sometimes fatal illness.

“When you’re fifty-five years old and you’re wearing diapers that you’re changing ten times a day,” Matt Hamilton says, “you’re numb to the ick factor.” He lifts some stuffed tomatoes to his plate. Matt has the forceful, unabashed appetite of the big, young male.

“For the patient, there is no ick factor,” Khoruts adds. “They’ve been icked out. It’s a chronic disease and they just want to be rid of it.”

As regards bacteria in general, a radical shift in thinking is under way. For starters, there are way more of them than you. For every one cell of your body, there are nine (smaller) cells of bacteria. Khoruts takes issue with the them-versus-you mentality. “Bacteria represent a metabolically active organ in our bodies.” They are you. You are them. “It’s a philosophical question. Who owns who?”

People’s bacterial demographics are likely to influence their day-to-day behavior. “Certain populations in the gut may want you to eat a certain kind of diet or to store energy differently.” (A clinical trial is under way in the Netherlands to see if transplants of “donor feces” from lean volunteers will help subjects lose weight;[119] thus far results are encouraging but undramatic.) Khoruts gave me a memorable example of how behavior can be covertly manipulated by microorganisms. The parasite Toxoplasma infects rats but needs to make its way into a cat’s gut to reproduce. The parasite’s strategy for achieving this goal is to alter the rat brain such that the rodent is now attracted to cat urine. Rat walks right up to cat, gets killed, eaten. If you saw the events unfold, Khoruts continued, you’d scratch your head and go, What is wrong with that rat? Then he smiled. “Do you think Republicans have different flora?”

What determines your internal cast of characters? For the most part, it’s luck of the draw. The bacteria species in your colon today are more or less the same ones you had when you were six months old. About 80 percent of a person’s gut microflora transmit from his or her mother during birth. “It’s a very stable system,” says Khoruts. “You can trace a person’s family tree by their flora.”

The party is winding down. I go into the kitchen to say good night to James and to Khoruts’s mirthful, tolerant girlfriend, Katerina. A blender sits on the counter by the sink, waiting to be washed. “Hey,” says James. “You missed the chocolate poop smoothies.”

That’s okay, because I’ll be seeing the real thing.

LIKE ANY TRANSPLANT, it begins with a donor. “Anyone’s will do,” says Khoruts. He has no idea which bacteria he’s after—which are the avenging angels that bring C. diff under control. Even if he knew, there’s no simple way to determine whether those species are present in a donor’s contribution. Most species of fecal bacteria are tough to culture in the lab because they’re anaerobic, meaning they can’t live in the presence of oxygen. (Common strains of E. coli and Staph bacteria are exceptions. They thrive inside people and out, on doctors and their equipment, and everywhere in between.)

The only thing Khoruts requires of donors is that they be free of digestive maladies and communicable diseases. Family members are not the most desirable donors because their medical questionnaire may not be entirely truthful. “You wouldn’t necessarily want to reveal to your loved ones that you’ve been visiting prostitutes.” Khoruts is partial to the donations of a local man who, understandably, wishes to remain anonymous. This man’s bacteria have been transplanted into ten patients, curing all of them. “His head is getting bigger,” deadpans Khoruts. Most of what Khoruts says is delivered deadpan. “In Russia,” he told me, “if you smile a lot, they think something’s wrong with you.” He has to remind himself to smile when he talks to people. Sometimes it arrives a beat or two late, like the words of a far-flung foreign correspondent reporting live on TV.

“Here he is.” A tall man, dressed for a Minneapolis winter, lopes down the hallway carrying a small paper bag.

“Not my best work,” the man says, nodding hello to me as he hands Khoruts the bag. With no further chitchat, he turns to leave. He does not seem embarrassed, just pressed for time. He’s an unlikely hero, quietly saving lives and restoring health with the product of his morning toilet.

Khoruts slips into an empty exam room and dials Matt Hamilton’s number. On the morning of a transplant, Matt will stop by the hospital on his way to the Environmental Microbiology Laboratory, where he works and the material is processed. He’s usually here by now, and Khoruts is feeling antsy. Anaerobic bacteria outside the colon have a limited life span. No one knows how many hours they can survive.

Khoruts leaves a message: “Hi, it’s Alex. The stuff is ready for pickup.” He squints. “I think that’s his number.” It would be a provocative message to receive from a stranger. I picture narcotics officers storming the gastroenterology department, Khoruts struggling to explain.

Khoruts has barely hung up when Matt hustles in, all polar fleece and apology. Matt smiles as naturally as Khoruts doesn’t. I imagine it is almost impossible to be peeved at Matt Hamilton.

The lab is ten minutes by car. Because Matt is driving fast and the cooler keeps threatening to slide off the backseat, there’s a mild tension in the car. The cooler is a tangible presence, somewhere between groceries and an actual passenger. Soon we’re circling, looking for parking. Matt resents the waste of time. “If I had organs, they’d give me a parking pass.”

The parking turns out to take longer than the processing. The equipment is simple: an Oster[120] blender and a set of soil sieves. The blender lid has been rigged with two tubes so that nitrogen can be pumped in and oxygen forced out. Two or three 20-second pulses on the liquefy setting typically does the trick, and then it’s on to the sieves. For obvious reasons, everything is done under a fume hood. Matt chats as he sieves, occasionally calling out a recognizable element: a chili flake, a piece of peanut.[121]

A decision is made to do a second run through the blender. If the material doesn’t flow freely, it can clog the colonoscope and compromise the microbes’ spread through the colon. He turns to face me. “So today we’ve kind of been confronted with what to do when it’s a hard, solid chunk rather than an easier mix.” It’s like American Chopper when Paul Sr. or Vinnie addresses the camera to give a summary of what viewers have been seeing.

Finally the liquid is poured into a container with a very good seal and returned to the cooler. It looks like coffee with low-fat milk. There is almost no smell, the gases having all gone up the fume hood. The three of us, Matt and I and The Cooler, hurry back to the car and retrace our route to the hospital.

The transplant patient has arrived. He waits on a gurney in a room made by curtains. Khoruts is in the hallway in his white coat. Matt hands him the cooler. He fills and caps four vials that will be pumped into the patient through the colonoscope. For now, they are laid on ice in a plastic bowl. Khoruts asks a passing nurse where he can leave the bowl while he waits for an exam room to open up. She glances at it, barely breaking stride. “Just don’t bring it in the break room.”

LIKE PEOPLE, BACTERIA are good or bad not so much by nature as by circumstance. Staph bacteria are relatively mellow on the skin, presumably because there are fewer nutrients there. Should they manage to make their way into the bloodstream via, for instance, a surgical incision, it’s a different story. Receptors and surface proteins allow bacteria to “sense” nutrients in their environment. As Matt puts it, “They’re like: ‘This is a good spot, we should go crazy in here.’” Gut microflora party! Bad news for the host. Strains found in hospitals are more likely to be antibiotic-resistant, and hospital patients are often immunocompromised and can’t fight back.

Likewise E. coli. Most strains cause no symptoms inside the colon. The immune system is accustomed to huge numbers of them in the gut. No cause for alarm. Should the same strain make its way to the urethra and bladder, now it’s perceived as an invader. In this case, the immune attack itself creates the symptoms—in the form, say, of inflammation.

Even C. difficile is not inherently bad. Thirty to fifty percent of infants are colonized with C. diff and suffer no ill effects. Three percent of adults are known to harbor it in their gut without problems. Other bacteria may tell it not to make toxins, or the numbers are too small for the toxins to create noticeable symptoms.

The problems often begin when a colon is wiped clean by antibiotics. Now C. diff has a chance to gain a foothold. As careful as hospitals try to be, C. diff spores are everywhere. And certain conditions in the colon make it easier for C. diff to thrive. Diverticuli are pockets along the colon wall, often created by chronic constipation. Like this: If the muscles of the colon have to push hard to move waste along and there’s a weak spot in the wall, the matter will follow the path of least resistance. The weak spot will balloon outward and form a small pocket. C. diff spores seed the pockets.

Eighty percent of the time, antibiotics clear up a C. diff infection. Twenty percent of the time, it comes back within a week or two. The C. diff entrenched in diverticuli are tough to annihilate; they’re the Al Qaeda of the GI tract, hiding out in inaccessible caves. “Antibiotics are a double-edged sword,” says Khoruts. “They suppress C. diff, but they also kill the bacteria that keep it under control.” Every time the patient has a relapse, the chance of another relapse doubles. Infections with C. diff kill around sixteen thousand Americans a year.

Today’s patient has diverticuli that became abscessed. Multiple severe bouts of colitis have caused diarrhea so severe he has had, at times, to be fed intravenously. You wouldn’t guess any of this to look at him now, in the exam room. He has been given Versed, an antianxiety medication. He lies calmly on his side in a blue and white johnny with no pants. There is a heartbreaking vulnerability to people having hospital procedures. They may be CEOs or generals on the outside, but in here they are just patients, docile, hopeful, grateful.

The lights are dim and a stereo plays classical music. Khoruts makes conversation to gauge the sedative’s effects. He’s listening for a quieting of the voice, a slowing of words. “Do you have any pets?”

The room is quiet for a moment. “…pets.”

“I think we’re ready to go.”

A nurse brings the bowl with the vials. I ask her if the red color of the caps on the vials signifies biohazard.

“No, just the brown color inside.”

Unless one is watching closely, a fecal transplant looks very much like a colonoscopy. The first thing to appear on the video monitor is a careering fish-eye view of the exam room as the scope is pulled from its holder and carried over to the bed. If you are young enough to be unfamiliar with a colonoscope, I invite you to picture a bartender’s soda gun: the long, flexible black tube, the controls mounted on a handheld head. Where the bartender has buttons for soda water and cola, Khoruts can choose between carbon dioxide, for inflating the colon so he can see it better, and saline, for rinsing away remnants of an “inadequate prep.”

Khoruts works the control buttons with his left hand, torquing the tube with his right. I comment that it’s like playing an accordion or a piano, both arms working independently at unrelated tasks. Khoruts, who plays piano in addition to colonoscope, prefers the analogy of the amputee’s prosthesis. “Over time it becomes part of your body. Even though I don’t have nerve endings there, I kind of know what’s happening.”

We’re in now, heading north. The man’s heartbeat is visible as a quiver in the colon wall. Khoruts maneuvers a crook. Shifting a patient’s position can help unkink a sharp turn, so the nurse leans in hard, like a driver pushing a stall to the shoulder of the road.

Using a plunger on the control head, Khoruts releases a portion of the transplant material. Since the colon has been wiped clean beforehand with antibiotics, the unicellular arrivals won’t have to battle a lot of natives. However many survived the antibiotic, the immigrants are sure to prevail. Within two weeks, Khoruts’s research shows, the microbial profiles of donor and recipient colons are synced.

One more release, at the far end of the colon, and Khoruts retracts the scope.

A couple days later, Khoruts forwards an e-mail from the patient (with surname deleted). The pain and diarrhea that had kept him from going to work for a year were gone. “I had,” he wrote, “a small solid bowel movement on Saturday evening.” It may not be your idea of an exciting Saturday evening, but for Mr. F., it was tough to top.

THE FIRST FECAL transplant was performed in 1958, by a surgeon named Ben Eiseman. In the early days of antibiotics, patients frequently developed diarrhea from the massive kill-off of normal bacteria. Eiseman thought it might be helpful to restock the gut with someone else’s normals. “Those were the days when if we had an idea,” says Eiseman, ninety-three and living in Denver at the time I wrote him, “we simply tried it.”

Rarely does medical science come up with a treatment so effective, inexpensive, and free of side effects. As I write this, Khoruts has done forty transplants to treat intractable C. diff infection, with a success rate of 93 percent. In a University of Alberta study published in 2012, 103 out of 124 fecal transplants resulted in immediate improvement. It’s been fifty-five years since Eiseman first pushed the plunger, yet no U.S. insurance company formally recognizes the procedure.

Why? Has the “ick factor” hampered the procedure’s acceptance? Partly, says Khoruts. “There is a natural revulsion. It just doesn’t seem right.” He thinks it has more to do with the process by which a new medical procedure goes from experimental to mainstream. A year after I visited, the major gastroenterology and infectious disease societies invited “a little band of fecal transplant practitioners” to put together a “best practice” paper outlining optimal procedures: a common first step toward establishing codes for billing for the procedure and making the case for insurance companies to cover it. As of mid-2012, there was no billing code or agreed-upon fee. Khoruts estimates the process will take one to two years more. In the meantime, he simply bills for a colonoscopy.

The extent to which health care bureaucracy stands in the way of better patient care is occasionally astounding. It took a year and a half for Khoruts’s study on bacteriotherapy for recurrent C. diff infection to be approved by the University of Minnesota’s Institutional Review Board (IRB)—which oversees the safety of study subjects—even though the board had no substantive criticisms or concerns. The morning I visited to see the transplant, Khoruts showed me an object I wasn’t familiar with, a winged plastic bowl called a toilet hat[122] that fits over the rim of the bowl to catch the donor’s produce. “That caused about two months of delay on the IRB protocol,” he said. “They sent it back saying, ‘Who’s going to pay for the toilet hats?’ They’re fifty cents apiece.”

Khoruts has also been working on a proposal for a study to evaluate fecal transplants for treating ulcerative colitis.[123] Inflammatory bowel diseases—irritable bowel syndrome, ulcerative colitis, Crohn’s disease—are thought to be caused by an inappropriate immune response to normal bacteria; the colon gets caught in the cross fire. This time around, the IRB refused to approve the trial until the FDA had approved it. And that’s just for the trial. Final FDA approval, the kind that makes the procedure available to anyone, is a costly process that can take upward of a decade.

And in the case of fecal transplants, there’s no drug or medical device involved, and thus no pharmaceutical company or device maker with diverticuli deep enough to fund the multiple rounds of controlled clinical trials. If anything, drug companies might be inclined to fight the procedure’s approval. Pharmaceutical companies make money by treating diseases, not by curing them. “There’s billions of dollars at stake,” says Khoruts. “I told Katerina, if this works, don’t be surprised to find me at the bottom of the river.”

We are sitting in Khoruts’s office, in between colonoscopies. Above our heads, on a shelf, is a lurid plastic life-size model of a human rectum afflicted by every imaginable malady: hemorrhoid, fistula, ulcerative colitis, fecaliths. Metaphor for the U.S. health care system?

Khoruts smiles. “Bookend.” A drug company was giving them away at Digestive Disease Week, an annual convention of gastroenterologists and drug reps, with the occasional person dressed as a stomach, handing out samples.

While the bureaucracy inches forward, fecal transplants for C. diff are quietly carried out in hospitals in thirty states. But that leaves twenty where patients have no access. Some have turned to what a researcher in one Clinical Gastroenterology and Hepatology paper called “self-administered home fecal transplantation.” Though seven of seven C. diff sufferers were cured by self- or “family-administered” transplants using a drugstore enema kit, it doesn’t always go well. One woman who recently e-mailed Khoruts for advice didn’t follow directions. She put tap water in the blender, and the chlorine killed the bacteria. Another in-home transplant replaced one source of diarrhea with another: fecal parasites contracted from the donor. Rather than protecting patients, IRBs—with their delays and prodigious paperwork—can put them in harm’s way.

Fecal bacteriotherapy will quickly become more streamlined. More sophisticated filtration will enable the separation of cellular material from ick. The bacteria can then be dosed with cryoprotectant—to prevent ice crystals from puncturing the cells—frozen, and shipped where it’s needed, when it’s needed. Khoruts’s operation is already headed this way.

The Holy Grail would be a simple pill, along the lines of the lactobacillus suppositories used to cure recurrent yeast infection. Generally and unfortunately, aerobic strains that are easy to grow and keep alive in the oxygen environment of a lab are unlikely to be the beneficial ones. Though researchers don’t know exactly which bacteria are the desirables, they do know they’re likely to be anaerobic species that thrive only within the colon. You want the creatures that are dependent on a healthy you for their own survival, the ones whose evolutionary mission is aligned with your own—your microscopic partners in health.

I asked Khoruts what exactly is in the “probiotic” products seen in stores now. “Marketing,” he replied. Microbiologist Gregor Reid, director of the Canadian Research & Development Centre for Probiotics, seconds the sentiment. With one exception, the bacteria (if they even exist) in probiotics are aerobic; culturing, processing, and shipping bacteria in an oxygen-free environment is complicated and costly. Ninety-five percent of these products, Reid told me, “have never been tested in a human and should not be called probiotic.”

I PREDICT THAT ONE way or another, within a decade, everyone will know someone who’s benefited from a dose of someone else’s body products. I recently received an e-mail from a doctor in Texas, telling me the story of Lloyd Storr, a Lubbock physician who treated chronic ear infections via homemade “earwax transfusions”: drops of donor earwax boiled up in glycerin. Earwax maintains an acid environment that discourages bacterial overgrowth and possibly contains some antibacterial chemicals. Whatever it does, some people’s works better than others’. Khoruts has been encouraging a friend of his, a periodontist, to try bacterial transplantation[124] as a treatment for gum disease.

If things go as they should, the bacteria hysteria so lucratively nurtured by the likes of Purell and Lysol will begin to subside. Thanks to the courageous blender-wielding pioneers of bacterial transplantation, fussiness and unfounded fear will be buffered by rational thinking and perhaps even a modicum of gratitude.

A tip of the toilet hat to you, Alexander Khoruts.

THE GREAT IRONY is that in the beginning, the gut was all there was. “We’re basically a highly evolved earthworm surrounding the intestinal tract,” Khoruts commented as we drove away from his clinic the last day I was there. Eventually, the food processor had to have a brain attached to help it look for food, and limbs to reach that food. That increased its size, so it needed a circulatory system to distribute the fuel that powered the limbs. And so on. Even now, the digestive tract has its own immune system and its own primitive brain, the so-called enteric nervous system. I recalled what Ton van Vliet had said at one point in our conversation: “People are surprised to learn: They are a big pipe with a little bit around it.”

You are what you eat, but more than that, you are how you eat. Be thankful you’re not a sea anemone, disgorging lunch through the same hole that dinner goes in. Be glad you’re not a grazer or a cud chewer, spending your life stoking the furnace. Be thankful for digestive juices and enzymes, for villi, for fire and cooking, all the miracles that have made us what we are. Khoruts gave the example of the gorilla, a fellow ape held back by the energy demands of a less streamlined gut. Like the cow, the gorilla lives by fermenting vast quantities of crude vegetation. “He’s processing leaves all day. Just sitting and chewing, and cooking inside. There’s no room for great thoughts.”

Those who know the human gut intimately see beauty, not only in its sophistication but in its inner landscapes and architecture. In a 1998 issue of the New England Journal of Medicine, two Spanish physicians published a pair of photographs: “the haustrations of the transverse colon” side by side with the arches of an upper-floor arcade in Gaudi’s La Pedrera. Inspired, wanting to see my own internal Gaudi, I had my first colonoscopy without drugs.[125]

There is an unnameable feeling I’ve had maybe ten times in my life. It is a mix of wonder, privilege, humility. An awe that borders on fear. I’ve felt it in a field of snow on the outskirts of Fairbanks, Alaska, with the northern lights whipping overhead so seemingly close I dropped to my knees. I am walloped by it on dark nights in the mountains, looking up at the sparkling smear of our galaxy. Laying eyes on my own ileocecal valve, peering into my appendix from within, bearing witness to the magnificent complexity of the human body, I felt, let’s be honest, mild to moderate cramping. But you understand what I’m getting at here. Most of us pass our lives never once laying eyes on our organs, the most precious and amazing things we own. Until something goes wrong, we barely give them thought. This seems strange to me. How is it that we find Christina Aguilera more interesting than the inside of our own bodies? It is, of course, possible that I seem strange. You may be thinking, Wow, that Mary Roach has her head up her ass. To which I say: Only briefly, and with the utmost respect.