Stool transplants highly efficient for Clostridium difficile infections and other gastrointestinal conditions — online press conference at 2nd World Summit “Gut Microbiota For Health” held today
(26 February 2013) Clostridium difficile infections have developed into a virtual pandemic over the past two decades. The outcome of standard antibiotic treatment is unsatisfactory: the recurrence rates are high with every relapse increasing the risk of further follow-ups. Faecal microbiota transplantation offers a rapidly acting and highly effective alternative in treating recurrent Clostridium difficile infections (RCDI), as Professor Lawrence J. Brandt (Montefiore Medical Center, New York, USA) points out. According to him, more than 90 per cent of the patients are being cured within a short period of time. This is one of the topics presented at the 2nd World Summit “Gut Microbiota For Health” in Madrid, Spain. Since 24 February 2013, internationally leading experts have been discussing the latest advances in gut microbiota research and its impact on health.
The number of gut infections through toxins released by Clostridium difficile bacteria has strongly increased over the past two decades. Patients suffer from diarrhoea, sometimes accompanied by fever and abdominal pain. In severe cases, such an infection can even develop into a life-threatening condition. C. difficile bacteria, which populate the guts of many individuals, do no harm as long as they are held in check by other kinds of intestinal bacteria that form part of the human gut microbiota. But certain antibiotic treatments can disturb this balance by reducing the number of these competitors and thus letting the amount of C. difficile bacteria grow disproportionately. It is this dominating role of C. difficile within the gut microbiota composition that fosters the production of toxins and causes the disease.
Restoring the balance
Standard treatment of C. difficile infections includes the cessation of the offending antibiotic, if possible, and the administration of metronidazole or vancomycin, which means that a disease that has been induced by antibiotics is being treated by the intake of other antibiotics. “Most patients initially respond to this treatment, but the risk of recurrence is 10 to 20 per cent,” says Prof. Brandt. “And in patients who have one recurrence, the chance of a second one is up to 45 per cent and of those patients who have a second recurrence, the chance of a third recurrence is up to 65 per cent.” There is evidence that the gut microbiota in patients with RCDI is altered not only temporarily, but also on a more permanent basis. As Prof. Brandt points out, studies of these patients’ faecal microbiota have shown that they have a marked decrease in the diversity of their gut microbiota and especially the phyla Bacteroidetes and Firmicutes compared with the microbiota in normal patients and those who have had just one episode of C. difficile infection.
RCDI is difficult to treat and doctors usually resort to additional courses of metronidazole or vancomycin although with rather mixed results as the high recurrence rates show. “An alternative therapy is urgently needed and faecal microbiota transplantation (FMT) has proven to be highly beneficial as its cure rates, according to international studies, exceed 90 per cent worldwide,” says Prof. Brandt. The healing effects of the treatment show up early and remain permanent in the great majority of cases.
The principle underlying FMT is the restoration of a balanced microbiota through faeces of healthy donors that contain the kinds of bacteria the patient’s gut microbial community is lacking. The procedure as such has long been known and had already been applied in China since the fourth century for various kinds of gastrointestinal diseases. As regards modern times, the first use of FMT for treatment of RCDI dates back 30 years. While, at the time, enemas were the most common technique of administering the donor faeces, a variety of additional methods of faecal infusion have been developed since, including colonoscopy, as well as tubes that use the route through the nose into the stomach or the duodenum.
“So far, FMT via colonoscopy or enema has proven more successful for RCDI than using the nasogastric route, which with an overall resolution rate of 80 per cent remains slightly below the average outcome,” says Prof. Brandt. Recently, results of a randomised controlled trial were published of FMT administered by nasoduodenal tube, compared with vancomycin alone and with bowel lavage. In this trial, the cure rate for RCDI was 81 per cent after one FMT and 94 per cent after two FMTs compared with 31 per cent and 23 per cent in the vancomycin arms of the study.
Suitable for a broad range of disorders
How is the transplantation actually carried out? Before administering the faeces, the donor’s stool — for the sake of the patient’s safety — has to be tested for infectious agents. In order to produce a suspension that can be infused, the stool is then mixed with milk, water or saline and filtered to prevent obstruction of the tube or endoscope’s accessory channel, which serves as a ‘pipeline’ for the faeces.
“The amount of stool to be used has not been standardised, although those given to weighing and measuring rather than just ‘eyeballing’ the product’s appearance favour 50g in 250cc of diluent,” says Prof. Brandt. “It seems as if more is better and most ‘FMTers’ are now using about 300cc for colonic FMT and 60cc for the upper FMT route.” To make sure that they hold the administered stool for at least four, preferably six hours, the patients take a drug against diarrhoea before the procedure starts. Regardless of the chosen route of infusion, FMT seems to be a safe method, with no negative side effects or complications reported so far.
Although RCDI therapy is the major field of FMT application to date, it has also been used successfully to treat inflammatory bowel disease, irritable bowel syndrome, obesity and chronic constipation. Even in a number of non-GI related diseases such as Parkinson’s, chronic fatigue syndrome and autism, FMT has shown to be helpful. The fact that this broad range includes neurological disorders lends additional support to the claim that brain, gut and microbiota are closely connected through an axis formed by a multitude of interrelated paths.
“So far, much of what we know about FMT is based on practical experience. We need to explore in detail the effects the different varieties of this treatment have on the whole spectrum of disorders that we are dealing with,” says Prof. Brandt. “But it is already plain that this new — and at the same time old — technique has a great potential for the patients’ benefit.”
About the Gut Microbiota & Health Section of ESNM
ESNM stands for the European Society of Neurogastroenterology and Motility, a member of United European Gastroenterology (UEG). The mission of the ESNM is to defend the interests of all professionals in Europe involved in the study of neurobiology and pathophysiology of gastrointestinal function. The Gut Microbiota & Health Section was set up to increase recognition of the links between the gut microbiota and human health, to spread knowledge and to raise interest in the subject. The Gut Microbiota & Health Section is open to professionals, researchers, and practitioners from all fields related to gut microbiota and health. www.esnm.eu/gut_health/gut_micro_health.php?navId=68
About the AGA
The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programmes of the organisation. www.gastro.org
About Danone Dairy and Gut Microbiota For Health
Danone’s conviction is that food plays an essential role in human health namely through the impact that gut microbiota may have on health. That is why Danone Dairy supports the Gut Microbiota For Health World Summit and Experts Exchange web platform with the aim to encourage research and increase knowledge in this promising area, in line with its mission to “bring health through food to as many people as possible”.
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