Microbiota as a therapeutic option: not only in gastroenterology

Curing malignant melanoma with a faecal transplant may sound far-fetched, but new study results show the potential of microorganisms.

Microbiota and microbiome

All the bacteria we carry inside us weigh an impressive 2 kg. That is more than the brain (approx. 1.5 kg) and about as much as the human liver weighs. The fact that the microorganisms in the human body are not only comparably heavy, but also have a similar importance as an organ, is a rather recent discovery. However, it is still unclear how dysbioses of the intestinal microbiota play an important role in numerous diseases and if, conversely, their targeted modulation could be an effective therapeutic approach. However, applications are still limited.

What are the options for microbiota modulation?

So far, there are essentially two ways of favourably influencing the composition of microorganisms:

  1. With probiotics: These are preparations that contain living microorganisms such as bacteria or fungi as a therapeutic agent. Well-known examples include Escherichia coli Nissle 1917 or the yeast Saccharomyces boulardii.
  2. By means of faecal microbiota transplantation (FMT): This involves transferring the stool of a donor into the intestine of a (diseased) recipient. What exactly causes the positive clinical effects is not yet fully understood. However, FMT is used for recurrent Clostridioides difficile colitis with success rates of 70-95%, and is recognised as the treatment of choice for this indication in European guidelines and by the US Food and Drug Administration (FDA).

In which diseases does an altered microbiome play a role?

In addition to C. difficile colitis, there are numerous other diseases that are associated with a dysbiosis of the microorganisms. These include chronic inflammatory bowel disease, irritable bowel syndrome or intestinal graft-versus-host disease in the context of allogeneic stem cell transplantation. Here too, some positive effects of FMT have been achieved in studies, but these have not yet been confirmed.

The effect of probiotics on certain diseases is better documented. For example, Escherichia coli Nissle 1917 is authorised for maintaining remission in patients with ulcerative colitis. Studies have shown it to be as effective as mesalazine. Saccharomyces boulardii, on the other hand, has been shown to be effective in acute diarrhoea. It can alleviate and shorten the symptoms, especially in children, by rebalancing the microbiome.

However, the importance of our microscopic co-inhabitants goes far beyond the gastrointestinal tract. This is demonstrated by therapeutic successes in hepatic encephalopathy, neuropsychiatric diseases, and also in malignant melanoma. Current efficacy studies have indeed shown that FMT achieves positive effects in melanoma patients who are refractory to therapy. Patients with metastasised skin cancer who did not respond to immunotherapy were included. Around a third of them became therapy responders after stool transplantation.

Conclusions for medical practice

The human microbiome and microbiota-oriented therapies are a fascinating field of research. The pathophysiological relationships and the mechanisms behind the individual therapeutic approaches are only just beginning to be understood. However, the clinical successes to date already indicate the great potential of microbiota as a therapeutic option.