The cancer microbiome: Bacteria and cell interactions prove interesting for tumor diagnostics

Our microbiome equally influences health and disease; and could play a role in cancer development, therapy success, or tumour progression.

Host-bacteria interactions come into focus

The human microbiome influences health and disease in equal measure. In oncology, it could play a role in the development of cancer as well as in the success of therapy or tumour progression. This makes the human microbiome equally interesting for tumour diagnostics.

The reciprocal relationship between humans and the microbiome is still largely misunderstood. However, studies are increasingly providing evidence that the interplay between bacteria and the body can influence nutrient uptake, metabolic processes, inflammation and immune defences, even behaviour. This influence, for example on the development of cancer, could be direct (i.e. the pathogen causes tumours) or indirect (i.e. metabolic products or inflammation lead to cancer).

Indirect microbiome effects on tumour development

It is known, for example, that the microbiome can influence the metabolism or is itself changed by certain disease states. For example, we know from overweight patients that they have a different microbiome composition than normal-weight patients. The same can be observed in mice: There it was shown, among other things, that the "pathogenic properties" could be transferred from a donor mouse to a recipient mouse with the help of the microbiome (e.g. during stool transfer).

Metabolic products of some bacteria in the intestine can slow down the immune system, promote cell degeneration or lead to chronic inflammation, which are considered independent risk factors for cancer. For example, some commensal bacterial species in the human intestine are able to break down bile acids, and the metabolites then pass through the intestine and blood into the liver, where they weaken the immune defence against cancer cells. Still other microbes metabolise androgens and form new hormonally active substances from them, which in turn could have an influence on the prostate.

In addition, there are findings that the microbiome could control moods and the emotional world as well as the reward system via metabolic products. It has been known for a long time that chronic depression, for example, weakens the immune system and can also promote the development of tumours. On the other hand, optimism and joie de vivre have an immune-strengthening and "life-prolonging" effect.

Direct microbiome influence on tumour development

The organs and tissues of our body are colonised with individually different bacterial communities, e.g. the intestinal microbiome, the vaginal microbiome, the skin microbiome or the lung microbiome. All these bacterial communities are in direct exchange with the neighbouring body cells and also cancer cells. However, exactly how this exchange takes place is still largely unknown.

One particular species of intestinal commensal, Bilophila wadsworthia, for example, metabolises bile acids and releases large amounts of hydrogen sulphide in the process. This has a carcinogenic effect and promotes the development of intestinal cancer.

On the other hand, intestinal bacteria also drift with metastases in the body and eventually find themselves in organs and tissues far from the intestine. This is known from experiments with mice for intestinal bacteria of the genus Fusobacterium. If the mice were subsequently treated with antibiotics, this slowed down the growth of the new tumour foci.

The microbiome and immunotherapy

The influence of the microbiome on the therapy of a tumour disease is also particularly interesting. Especially, so-called immunotherapy, such as checkpoint inhibition, has been included in the treatment regimen for a number of tumours in recent years. In simple terms, this method is based on the fact that the "brake of the immune defence" realised by a tumour cell is released again by blocking the ligand-receptor interaction necessary for this. This enables the body's own immune system to attack the respective tumour again.

It is already known from studies that the microbiomes of people who responded to checkpoint inhibitors differ from those of people who did not. In addition, work on mice models has shown that antibiotic-treated mice responded less well or not at all to such immunotherapies due to damage to the skin microbiome. The same was true for animals that no longer had a skin microbiome.

In addition, it became known in this context that some commensal bacterial species release short chain fatty acids (SCFA), which in turn can promote the "pathogen memory" of CD8-positive T-lymphocytes and thus indirectly increase the immune response.

Conclusion

The interactions between the microbiome and human cells, including cancer cells, are multifaceted. Still, little is known about the direct and indirect factors of influence of the microbiome on tumorigenesis as well as oncological therapy. At the same time, the burden of tumour diseases is likely to increase in the future, so that many people will then have a high risk of developing a tumour.

Knowledge about this interaction between bacteria and body cells will therefore become increasingly important. On the one hand, the microbiome and its composition can be markers of which patients are particularly at risk of developing a tumour. On the other hand, therapies could be positively influenced with the help of the microbiome or individual components. This would ultimately improve tumour treatment on an individual basis. But until then, many more studies are needed in the field of microbiome research in oncology.

Original publication:
Xavier JB et al, The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View. Trends Cancer 2020; 6(3): 192-204. doi:10.1016/j.trecan.2020.01.004

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