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Microbes, faeces, and you

Cancer immunotherapy is a growing field of research as patients increasingly seek personalised treatments for complicated conditions — including faecal microbial transplants.

Image Credit: Coalition for Life Sciences

Microbes, generally defined as microorganisms, are ubiquitous – wherever life goes, they follow. Some cause disease while others are essential for digesting certain foods. For example, cellulose (found in plants) is indigestible for humans without the help of specialised microbes which degrade and transform it into digestible molecules.

There are many sites within the body that develop into microbiomes by cultivating specific types of microorganisms. Fun fact: the human body contains more microbial cells than human cells, most notably in the gut, the throat, and on the skin. When bacteria are in the right place and at the right concentration, the body seamlessly continues its daily functions. However, when microbiomes have too many bacterium — or when foreign bacterium triggers an immune response —  the body suffers.

A person’s microbiome plays an essential role in the development of their immune system. For instance, a child who is exposed to many germs and food types from a young age is able to acclimate to a normal level of microbes as an adult. Additionally, the immune system learns and recognises when to step in and kill excess bacteria.

A 2010 study revealed that diseases related to abnormal immune system function are becoming increasingly common in the Western world. The common thread is that our food is increasingly processed and devoid of difficult-to-digest nutrients (such as fibres and cellulose). In contrast, communities that consume traditional plant-based diets (like those in rural Burkina Faso), a child’s microbiota is completely different. Ultimately, this leads to lower incidences of chronic disease.

Our immune systems have been further weakened by antibiotic overprescription. This can weaken the body’s natural response to other dangerous pathogens over time and lead to internal organ inflammation, lesions, and even death from severe infections. Clearly, there is a need for an alternative mode of treatment. 

This is where the discussion of microbiomes comes in. Individuals with clostridium difficile bacterial infection — a disease causing inflammation of the colon and intense gastrointestinal symptoms — can be treated and managed by manipulating the preexisting microbiome of a patient. By taking a piece of someone else’s healthy gut microbiome and transplanting it into a patient infected with clostridium difficile, doctors can strengthen a patient’s immune response and simultaneously cure their illness. 

But how do you go about transplanting a complex system of thousands of microbes? Well, through the natural product of the gastrointestinal system – faeces.

Given the strong link between the immune system and one’s microbiome, doctors have begun investigating how manipulating the level of microbes in the gut may influence the body’s response to other treatments, including immunotherapy.

Immunotherapy is a growing field of research in which doctors manipulate the actions of the body’s own cells to fight cancer. The insidious nature of cancer is two-pronged. It causes tumour growth and simultaneously inhibits the body’s ability to fight them by hijacking the body’s natural response mechanisms. Cancer patients are thus more susceptible to other diseases too. Regaining control of the immune system through immunotherapy is hence a promising avenue for fighting cancer and its ancillary health complications. However, very few patients respond to treatment.

Fortunately, faecal microbiota transplants (FMT) may also be able to increase immunotherapy response rates. A recent trial in melanoma patients involved FMT from people who previously responded strongly to a specific type of immunotherapy to people who weren’t showing a strong improvement. The patients’ own immune systems were depleted using antibiotics, followed by a colonoscopy and the administration of an oral stool capsule. Three of nine patients saw a response to the treatment, with one experiencing a 100% shrinkage in their tumours.

When the gut microbiota of these patients was examined, they all showed an increased expression of genes related to the immune system, leaving them better able to combat the tumours. One patient even finished the 90-day trial with no remaining tumours. An interesting result of this pre-clinical (and therefore small-scale) trial was that the three patients who saw a decrease in cancer tumour mass received faecal transplants from the same donor. This suggests there may be some specific part of one’s microbiota that determines whether or not their faeces will be an effective treatment for enhancing responses to immunotherapy.

While researchers work to isolate the exact microbes, genes, and proteins that stimulate the immune system to fight cancer, Australian company BiomeBank has been collecting stool since 2013. Their samples are screened and preserved in-house before being sent off to gastroenterologists to treat tough cases of clostridium difficile

Microbiologists work to culture-specific strains of microbes associated with positive outcomes, collaborating with engineers and business people to develop stool-handling procedures and market the product to doctors. In its early days of development, a faecal transplant was particularly low-tech, with donations only going through rudimentary screening processes before transplant. However, as it evolves into a complete treatment, it is hoped that scientists will be able to culture single microbes to be made into an oral medicine. 

Microbes are ubiquitous, and their role within the body – whether it be innate, pathogenic or therapeutic – is essential. The field of cancer research is ever-growing, and any avenue that promises better outcomes for patients is worthwhile. The extreme nuance in every single case is a challenge that researchers can only surmount with increasingly personalised medicine. In pursuing this path, researchers should ensure they are investigating the diverse array of microbiomes present in people beyond Western and industrialised countries. The more alternatives offered to the greatest group of people, the better.