This is a standard party invitation in most respects: there’s a map of the neighbourhood, the address and time, and some friendly encouragement to bring the whole family. The decorative elements, though, are unusual: a cut-away illustration of the interior of the human colon, its parts neatly labelled. 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 colonoscopies and dyspepsia consultations, he performs transplants of colon bacteria – aka gut microflora. Almost everyone gathered at the party this evening is involved with this work.
Leaning into the buffet is Matt Hamilton, a University of Minnesota postdoctoral fellow who prepares the matter for transplant. Matt is spooning Khoruts’s homemade Russian red beet salad on to a plate, so much of it that a nurse tells him he’s going to “look like a GI bleed” tomorrow. The nurse admires a platter of whole, chocolate-covered bananas, one of the thematically appropriate desserts created by Khoruts’s 13-year-old son. James is very much his father’s son, intelligent and cultured, with a sly sense of humour. The nurse asks James what number the desserts would be on the Bristol stool scale. He replies without hesitating – four (“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 from the rest of us. The interactions between the human body and its gut microbiome – as our 100 trillion intestinal guests are collectively known – has been 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 the food down. One example is the cancer fighter du jour – the polyphenol family, found in coffee, tea, fruit and vegetables.
Some of the most beneficial polyphenols aren’t absorbed in the small intestine: we depend on colonic bacteria to metabolise them. Depending on what’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; the efficacy of a drug may vary, depending on the make-up of your gut flora.) The science is complex, but the bottom line is simple: changing people’s bacteria is a more effective strategy for treatment and prevention of disease than changing their diet.
You may find it disturbing to imagine checking into 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 Cdiff can be incapacitating and sometimes fatal.
“When you’re 55 and you’re wearing nappies that you’re changing 10 times a day, you’re numb to the ick factor,” says Matt Hamilton. “For the patient, there is no ick factor,” Khoruts adds. “They’ve been icked out. It’s a chronic disease and they just want rid of it.”
As regards bacteria in general, a radical shift in thinking is under way. For starters, there are far 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. They are you; you are them. “It’s a philosophical question: who owns whom?”
What determines your internal cast of characters? For the most part, it’s the luck of the draw. The bacteria species in your colon today are more or less the same you had when you were six months old. About 80% of a person’s gut microflora are transmitted from the 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 goodnight to James and to Khoruts’s 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 OK, because I’ll be seeing the real thing.
Like any transplant, it begins with a donor. “Anyone’s will do,” says Khoruts when we meet at the hospital. He has no idea which bacteria he’s after – which will bring Cdiff 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 faecal 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 staphylococcal 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 10 patients, curing all of them. “His head is getting bigger”, says Khoruts, deadpan. “Here he is.” A tall man, dressed for a Minnesota winter, lopes down the corridor carrying a small paper bag.
“Not my best work,” the man says, as he hands Khoruts the bag. With no further chitchat, he turns to leave. He’s an unlikely hero, quietly saving lives and restoring health with the product of his morning visit to the toilet.
Khoruts slips into an 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 lab, where he works and the material is processed. The equipment is simple: an ordinary kitchen 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 recognisable element, such as a chilli flake or a piece of peanut.
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. Matt 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.”
Finally, the liquid is poured into a container with a very good seal and placed in a cooler. It looks like coffee with semi-skimmed milk. There is almost no smell, the gases having all gone up the fume hood. With the cooler, we hurry back to the car and retrace our route to the hospital.
The transplant patient waits on a trolley in a room formed by curtains. Khoruts is in the corridor 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.
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 patients are often immuno-compromised 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, it’s perceived as an invader. In this case, the immune attack itself creates the symptoms – in the form, say, of inflammation.
Even Cdifficile is not inherently bad. About 30-50% of infants are colonised with Cdiff and suffer no ill effects; 3% of adults harbour it in their guts 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 Cdiffhas a chance to gain a foothold. As careful as hospitals try to be, Cdiff spores are everywhere, and certain conditions in the colon make it easier for it to thrive. Diverticuli are pockets along the colon wall, often created by chronic constipation. It’s 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 outwards and form a small pocket. Cdiff spores seed the pockets.
About 80% of the time, antibiotics clear up a Cdiff infection. About 20% of the time, it comes back within a week or two. The Cdiff entrenched in diverticuli are tough to annihilate; they’re the al-Qaida of the GI tract, hiding out in inaccessible caves. “Antibiotics are a double-edged sword,” says Khoruts. “They suppress Cdiff, 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 Cdifficile kill about 14,000 people in the US each year. Today’s patient has diverticuli that have become abscessed. Multiple severe bouts of colitis have caused diarrhoea so severe that he has, at times, had to be fed intravenously.
A faecal 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 unfamiliar with a colonoscope, picture a bartender’s soda dispenser – the long, flexible black tube, the controls mounted on a handheld head. Where the bartender has buttons for soda 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, applying torque to the tube with his right. I comment that it’s like playing an accordion or a piano, both arms working 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 manoeuvres a crook.
Using a plunger on the control head, Khoruts releases a portion of the transplant material. As the colon has been wiped clean with antibiotics, the unicellular arrivals won’t have to battle a lot of natives. However many have 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 in sync.
A couple of days later, Khoruts forwards an email from the patient (with surname deleted). The pain and diarrhoea that had kept him from going to work for a year was gone. “I had,” he wrote, “a small solid bowel movement on Saturday evening.” It may not be your idea of an exciting Saturday but, for Mr F, it was tough to top.
The first faecal transplant was performed in 1958, by Ben Eiseman. In the early days of antibiotics, patients frequently developed diarrhoea from the massive killing-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, 93 and living in Denver at the time I wrote to 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 40 transplants to treat intractable Cdiff infection, with a success rate of 93%. But only one doctor in the UK has stepped forward to say that he offers it. Why? Has the “ick factor” hampered the procedure’s acceptance? Partly, says Khoruts: “There is a natural revulsion. It just doesn’t seem right.” The findings of the first faecal transplant randomised clinical trial in which 94% of patients were cured compared with 27% who of those who were given antibiotics, should help to alter this situation. But there’s no drug or medical device involved. 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 in Khoruts’s office. On a shelf is a lurid, plastic, life-size model of a rectum afflicted by every imaginable malady – haemorrhoids, fistulae, ulcerative colitis, faecaliths. Is it a metaphor for the US healthcare system? Khoruts smiles, and says: “Bookend.”
Originally posted HERE