Life-saving microbes

Life-saving microbes
  • Faecal transplant is the most effective procedure to treat diarrhoea caused by the bacteria 'Clostridium difficile'. Experts are now studying how it could be used to treat obesity, depression and autism

For many animal species, eating excrement is a pleasure. Not only flies: elephants, pandas, cows, gorillas, rats, rabbits, dogs, iguanas, burying beetles and cockroaches do it as well. There is a reason for this: the intestinal bacteria present in a deposition aid digestion and strengthen the immune system. The creatures that eat faecal matter are known as coprophrages. In its own way, medicine imitates them, but removes the most repulsive aspect. Health systems have found transplanting faeces from a healthy person into a sick one a very effective way of curing persistent diarrhoea.

It is relatively easy for elderly people in hospital to become infected with the bacteria Clostridium difficile, a rebellious micro-organism which is very resistant to microbiotics. When the microbiota, a combination of bacteria, fungi, virus and archaea that reside in the human body, reach the patient's intestine, he or she only needs a day to recover after repeated evacuations. Without them, these problems would often result in a patient's death.

Victoria Pérez Robles, who is 85, can talk about her case thanks to her grandson, who was 20 years old at the time, because he donated faeces to be transferred to her. That was four years ago, when she was admitted to the Ramón y Cajal hospital in Madrid with a very high fever caused by a urinary infection.

"They let me go home, but I had to be admitted again because the diarrhoea and pains came back. I was going to the toilet 15 or 16 times a day and I lost 11 kilos. They did tests and found I had C. difficile," she says.

This elderly lady was bedridden and isolated in a hospital room for three months. The gastroenterologists and infectologists didn't really know how to treat her. They gave her antibiotics, but none had any effect, not even one which cost 2,000 euros for a full treatment. "They used to tell me I was taking gold," says Victoria.

Last resort

She had developed resistance to antibiotics because she had used them so much during her life to treat urinary infections which would occur every two weeks, ever since she had her second child. As a last resort, they decided to try a faeces transplant through colonoscopy. She was the second patient to undergo this treatment, faecal microbiota transplant (FMT) at the hospital.

"They did it on 30 August 2015 and I was able to go home on 1 September. Since then I haven't had a single urinary infection and I haven't had diarrhoea again," she says. Thanks to the transplant of faecal microbiota, Victoria was also freed from the bacteria which had been causing her frequent urinary infections.

What is really important is that this same faecal transfer technique could be effective in treating a wide range of problems, from obesity to irritable bowel syndrome, as well as autoimmune illnesses, depression and autism. There is still a great deal of research to be done, because at present there is a lack of scientific evidence.

So far, says Rosa del Campo, microbiologist at the Instituto Ramón y Cajal de Investigación Sanitaria (Irycis) in Madrid, it has been shown that there is a connection between the intestine and the brain.

"The metabolites of the bacteria can have a neurotransmission activity. It is something that has been quite well demonstrated in the scientific community. Everybody knows that sometimes, when you are nervous, you get diarrhoea," she says.

FMT is a simple, cheap and almost artisan procedure. It costs less than 100 euros to perform. "Beforehand, we talk to possible donors such as children and grandchildren, because when people live together there is always a crossover of bacteria and we can take advantage of that to make the patient's original microbiota recover. We need between 50 and 100 grammes of faeces from a relative. That material is mixed with half a litre of water and broken down through centrifugion so the colonoscope doesn't get blocked," says Rosa.

Capsules in the future

Scientific evidence has shown that faecal transplant is effective in 80 per cent of cases, and this rises to 94 per cent in the case of a reinfusion. Infection by Clostridium difficile is an important problem for hospitals, given that it reaches a prevalence of four cases per 10,000 patients a day, or three episodes per every 1,000 patients in hospital. The illness is on the increase because the population is ageing, a factor which results in more hospital stays and, with it, greater probability of coming into contact with the bacteria.

"There will be capsules in the near future, because colonoscopy is harmful in patients with an inflamed intestine, and also the patients tend to be very elderly," explains Rosa del Campo.

Irene Santos wasn't elderly when she suffered an attack by C. difficile. In fact, she was not even 40 when her brain ended up with no oxygen due to a malformation in her vascular system. She was working as a medical assistant at La Paz hospital in Madrid when she collapsed as a result of an arteriovenous fistula; in other words, her arteries were connected to her veins, in such a way that the former were supporting the CO2 supply. After that, she suffered a pulmonary infection while still in hospital, and acquired a very rare strain of C. difficile. Her weakened immune system made her especially vulnerable to the attack.

She then started to suffer from recurrent diarrhoea and was given a faecal transplant at the Ramón y Cajal hospital. Her mother, Celia Gómez, talks on her daughter's behalf, because Irene finds it difficult to speak because of the brain damage she suffered.

"I was scared when I heard the word 'transplant', because I was thinking of something major like a kidney transplant. Her father was the donor. They ruled me out, because I was taking omeprazol. The day after the colonoscopy, she was better," she says.

Despite the success of the FMT, Irene's problems continued because of her brain injury. "My daughter can't stand up, her hands have become somewhat atrophied, although she can use the computer a bit. She is having very intensive rehabilitation and, from a cognitive point of view, she's OK. We keep on fighting. Everything costs money, because these therapies are only available from private centres," says Celia.

Transplant or transfer

In the strictest sense, FMTs are not 'transplants' of faeces. 'Transfer' would be a better term. However, 'transplant' is the one that is normally used and it is official now. Also, faeces are not tissue and, as a result, this type of procedure is not covered by the National Transplant Organisation (ONT).

Scientist Ed Yong, author of the book 'Yo contengo multitudes' (published by Editorial Debate), who was responsible for microbes starting to be seen in a different way, defends the validity of the word. He says FMT "is a transplant of an ecosystem, an attempt to repair an unstable community by completely replacing it, in the same way that you would restore a lawn which has been invaded by dandelions".

The human body houses billions of microbes which form a world in symbiosis with its environment. They are as abundant as they are microscopic. One million of them could walk along the head of a pin. If this endless line of microorganisms were to group together, they would weigh two kilos.

The scientific community is excited by the therapeutic potential of benign bacteria, to such an extent that the Spanish Medications and Sanitary Products Agency (AEMPS) is prepared to regulate the therapy and classify it as a medication, at least to eradicate 'Clostridium difficile', as has been done in the US. Strictly speaking, classifying faecal material as a drug doesn't make sense, because the creation of a medication requires fixed production and that is impossible with FMT.

"The AEMPS wants to regulate it, but it is important to make sure it is only performed in hospitals and not just anywhere," explains Rosa del Campo.

Testing the bacteria

Because the technique is straightforward, some people have carried out their own transplants without laboratories being involved, and this is very dangerous because the process requires pathogens to be detected. If this is not done, there is the risk of serious infection.

The downside to FMT is that any long-term adverse effects are not known. The Ramón y Cajal hospital, a pioneer in this therapy, carried out its first procedure of this type in 2015. "We recently learned of the first death in the USA of someone who received this treatment because of a 'Clostridium difficile' infection and presented a bacteria which was multi-resistant to antibiotics," warns Rosa del Campo.

Although it is obligatory to check the absence of this type of micro-organism in donors, it seems that not everybody does so.

The omnipresence of processed foods in our diet is decimating the diversity of our microbes. From the studies which have been carried out on fossilised faeces, it appears that people from the preindustrial period had a much richer intestinal microbiota than those in the 21st century. They ate more plants and roots. In the old days, people didn't like the heavy dishes that are popular today, but their arsenal of metabolic resources to digest food was much more heterogeneous.