Faecal microbiota transplants: benefits and challenges

WHEN it comes to faecal microbiota transplantation (FMT), there is both good and bad news.

FMT is a procedure during which one person’s (healthy) gut bacteria are given to another person to treat bowel infection or inflammation. To do this, we must identify a healthy donor who can donate the stool that will be given to the patient. This is often a family member (because of patients’ preferences and convenience), although, increasingly, banks of organisms from healthy donors are being developed and used.

We must first ensure that the donor is healthy, by screening them to make sure they have not had any antibiotic exposure, or exposure to other drugs that might have affected their gut, in the prior 6 months. We need to ensure that the donor is not immunocompromised, and does not have chronic bowel disorders, a history of travel and other potential health issues.

We screen potential donors for infections (including infection with bloodborne viruses such as hepatitis B and C, and HIV) and colonisation with resistant organisms – once or multiple times. In general, the stool sample has to be collected and processed within about 6 hours – it can’t be sitting around for a long time. This is an intensive process.

The screening tests we currently use have their limitations, and have not been properly validated for stool. Furthermore, the tests we use to look for resistant or troublesome bacteria in the donor stool are the same as those used to detect actual infection, and may not identify small amounts of these bugs that could be present but are not causing infection. There is much interest at the Therapeutic Goods Administration at the moment in framing appropriate rules and regulations around how we screen FMT donors.

How is FMT prepared and administered?

Once the stool has been collected, it needs to be processed. It is mixed with a saline solution and then filtered. It can be administered and delivered to the small intestine via a gastroendoscope or to the colon via a colonoscope. It is usually delivered directly to the intestines and must bypass the stomach, as the stomach acids would destroy the bugs. Whether it is delivered to the upper or lower bowel is a medical decision, based on factors such as the degree of inflammation in the lower bowel or the presence of gastric reflux. There is a risk of regurgitation or aspiration with the gastro route of administration.

Adverse effects of FMT

It has been recognised that FMT treatment can have some adverse effects. Many patients who receive FMT to treat bowel infections report feeling better straight away. However, some people may experience diarrhoea, abdominal cramps, belching, constipation and fever. Although rare, people may also experience bowel perforation, and serious bacterial or fungal bloodstream infection. Things can go wrong, and it must be said that deaths (due to these adverse effects) have occurred after FMT. For those reasons, FMT is generally done in a controlled environment, in an operating theatre with an endoscopist and anaesthetist present.

When is it used as treatment?

FMT is effective in treating recurrent Clostridium difficile colitis (an infection that can occur after antibiotic treatment). FMT treatments have been widely and successfully used to treat recurrent C. difficile colitis in Europe. There are suggestions in the literature that FMT may also work against refractory C. difficile infection, when antibiotics have failed to control the infection.

There are a number of other conditions that are being treated with FMT but we don’t know about its efficacy in these diverse settings yet. There are some case reports about using FMT to treat colitis after immunotherapy but we still need more evidence before we can recommend it for this indication. FMT use is being investigated for some other gut diseases such as irritable bowel syndrome and inflammatory bowel disease, and even metabolic diseases such as diabetes.

We started looking into this area because a patient brought it up with us. They were about to start immunotherapy, and their question in the clinic was: “What can I do to improve my gut microbiota so that I can have the best chance of mounting a good response to immunotherapy?”

This patient was adamant about having FMT, and they did buy a product off the internet. We weren’t quite sure what it contained. What this example shows is that people are very interested in FMT and want information about it. As our patient was aware, in the cancer setting, gut microbiota health has been linked to response to immunotherapy.

One major difficulty is that the studies have all been done with slightly different methods, and there’s no one recipe. Nobody can tell us, “You’ve got to have 50% of this organism, and 20% of that, etc”. We don’t know what sort of microbiota composition may optimise the response to immunotherapy. What we do know, and our team wrote about this recently, is that a high level of diversity in the gut microbiota does improve the response to immunotherapy, and also has an influence on side effects from immunotherapy. There is some overlap between the microbiota composition that supports a good response and the microbiota composition that is associated with side effects, so we haven’t been able to identify the best composition for the best overall outcomes.

There is a phase 1 study underway in the US in which faecal matter from people who have responded well to immunotherapy is being transplanted into patients who have not. We are sure that there will be an attempt to identify the composition that might offer the best results.

We need to define what is a healthy gut microbiota, and we need more definitive information about microbiota composition for treating bowel infection, promoting the best response to cancer treatments, minimising the side effects of cancer treatments, and treating other bowel and metabolic conditions. We need studies that can help us identify how best to intervene and alter the gut microbiota to treat or prevent conditions. We also need agreement on how to select and screen donors, and on standardised procedures and licensing.

At the Peter MacCallum Cancer Centre in Melbourne, the oncology, gastroenterology and infection teams have planned a longitudinal study in which patients receiving immunotherapy will be followed over time so that we can examine changes in the gut microbiota associated with cancer therapies. Regular faecal and blood samples will be collected so that the impact of antibiotics on the microbiota, and the link to side effects of cancer treatment, and outcomes, can be examined. Research in this area is in its infancy.

Professor Monica Slavin is the head of infectious diseases and the director of the National Centre for Infections in Cancer at the Peter MacCallum Cancer Centre in Melbourne.

Dr Arjun Rajkhowa is the centre manager of the National Centre for Antimicrobial Stewardship at the Department of Medicine, University of Melbourne, the Doherty Institute, and Royal Melbourne Hospital in Melbourne.

Professor Karin Thursky is the deputy head of infectious diseases at the Peter MacCallum Cancer Centre in Melbourne; director of the National Centre for Antimicrobial Stewardship; director of the Guidance Group at the Royal Melbourne Hospital; and clinical lead of the statewide “Think sepsis, act fast” collaboration in Victoria (Better Care Victoria).

Dr Megan Crane is the centre manager of the National Centre for Infections in Cancer at the Peter MacCallum Cancer Centre in Melbourne.

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.