Unravelling the microbiome - health through happy communities

Through this series of articles, we’ll be taking a look at the seldom traversed world of Faecal Microbiota Transplantation (FMT). Join us as we delve into the science behind the concept and gradually examine how it can be applied to a wide range of gastrointestinal and infectious diseases such as Clostridium difficile (C. diff).

The human body – a vast ecosystem:

Host to trillions of microbial organisms which live on skin, for instance, on the surface of lungs and on the surface of the gut, this vast ecosystem includes bacteria, yeasts, fungi, viruses and protozoans, outnumbering our own cells 3 to 1. Acquired at birth and during the first couple of years of life, this microbiota or “microbiome” is maintained over a lifetime by interactions with the environment, food, and the drugs we use. There is growing evidence that the balance of communities it contains can directly affect the health of an individual. Take a situation where particular strains of “good” microbes are reduced or even eliminated, for example, allowing new or “bad” strains to take over. Researchers are turning up convincing pointers that altering the microbiome’s population balance in this way could directly impact health. Detailed mechanisms remain to be unpicked, but there is some evidence that the microbiome can influence the risk of suffering from cardiovascular disease, inflammatory or autoimmune diseases, diabetes, obesity, some cancers, or possibly even help trigger conditions like anxiety and depression, or play a role in disorders such as autism.

The quest for rebalance:

The last decade has seen an acceleration in interest in tools that can “rebalance” the microbiome, helped by genome sequencing tools. Now peptides, probiotics, bacteria and phages are all being investigated as potential ways to alter the microbiome’s constituency, and to reduce risk of disease [Ref 1].

So far, companies with therapies addressing gastrointestinal and infectious diseases such as Clostridium difficile (C. diff) have captured almost half of all investment. For now, the majority of the large pharmaceutical companies are not directly involved in microbiome R&D. But that's likely to change when positive clinical results start to appear.

Stool Sample Transfer:

Some of the earliest attempts to rebalance an individual's microbiome have involved the transfer of stool samples from a healthy donor into the gastrointestinal tract of the recipient, performed via colonoscopy, by a nasoduodenal tube or as a preparation inside a gel capsule. This is called Faecal Microbiota Transplantation (FMT). The idea is to replace pathogenic bacteria in the gut with healthy bacteria and this has shown promise in the treatment of recurrent and refractory gastrointestinal infections like those caused by C. diff. One study [Ref 2] showed that FMT is more effective than oral vancomycin in preventing further recurrences in individuals who have already had recurrent C. difficile colitis. In fact FMT is being explored in a wide range of indications, utilising a host of bacteria and microbes [Ref 3]. In the longer term, expect this focus to shift towards more specific groups of communities, or individual drugs aimed at suppressing or enhancing specific targets in the microbiome.

Currently, the FDA only allows the use of FMT without requiring an investigational new drug approval in recurrent C. difficile infection. But there are dozens of clinical studies investigating the impact of FMT on diseases such as diabetes, Crohn's and cirrhosis.

References
1. Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Celeste Allaband et al. Clinical Gastroenterology and Hepatology, online 18 September 2018 doi.org/10.1016/j.cgh.2018.09.017.
2. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. Els van Nood et al. N Engl J Med 2013; 368:407-415 doi: 10.1056/NEJMoa1205037.
3. Emerging Trends in “Smart Probiotics”: Functional Consideration for the Development of Novel Health and Industrial Applications. Racha El Hage Front Microbiol. 8: 1889. Sep 29. 2017 doi: 10.3389/fmicb.2017.01889.