In principle, we cannot be separated from our intestinal bacteria and they are of immense value to our well-being. Without these wonderful tiny organisms we wouldn’t be able to survive. They not only influence the way we take up nutrition and help break down complex fibers, but also have an impact on mood, personality and resilience to anxiety and stress. They produce a variety of hormones and neurochemicals similar to those of anti-anxiety drugs. Even further, our bacteria are actually able to turn our appetite on and off and influence what kind of food we are craving. Gut microbes manipulate our eating behavior in ways that promote their own fitness, sometimes at the expense of ours — quite self-serving! Especially, the microbial diversity is a key indicator of a healthy gut, as many different bacteria perform different tasks, and a diverse workforce brings more skills to the table.
Fewer than 100 species of bacteria cause diseases directly e.g. Clostridium difficile derived colitis, and hardly any microbes are known to enhance the risk for cancer, such as human papillomavirus (HPV), infamously known for its potential to induce tumor formation in the genital region. The thousands of types of microbes found in our gut are mostly harmless and vital for us. However, the composition of these bacteria needs to be balanced. Numerous studies increasingly indicate that a disturbed composition of intestinal bacteria is associated with a variety of diseases. Ulcerative colitis, Crohn’s disease, Alzheimers, Multiple Sclerosis, Psoriasis, Atherosclerosis, just to name a few, have all been linked to an altered gut microbiome.
Only very few microbes cause cancer directly (e.g. HPV), but many seem complicit in its growth, often acting through our immune system. Studies have shown differences in the intestinal microbiome compositions between patients with colorectal cancer (CRC) and healthy individuals meaning that specific microbes are more abundant or depleted in these patients. The direct relation remains unclear, however, inflammation, diet and oxidative stress play a key role in cancer formation. Fusobacterium nucleatum is a well studied bacterium which is associated with poor treatment outcome of CRC patients. It is thought that F. nucleatum attaches to the mucosal surface of the gut and induces oncogenic and inflammatory responses, altering the immune response and inducing tumor growth.
On the other hand, emerging evidence suggests that interactions between some gut bacteria and our immune system can have major anti-tumor effects. For example, in a melanoma immunotherapy-cohort, differences in the microbiome were identified between responders and non-responders to treatment. Specifically, patients with a more diverse gut microbiome and high abundance of Ruminococcaceae and Faecalibacterium had an enhanced response to therapy, mediated by increased antigen presentation and improved T cell function. In comparison, non-responders were associated with lower diversity and a high abundance of the bacterial order Bacteriodales. The mechanism remains unknown, however, the relationship between the intestinal microbiome and gut mucosa, and thus our immune system, plays a key role in efficient immunotherapy. This theory is supported by the fact that antibiotics, which alter microbial diversity, seem to reduce the efficacy of immunotherapy and decrease overall patient survival. Furthermore, transforming the microbiome by performing fecal microbiota transplant (FMT) (meaning transplanting donor stool to a recipient) increases the number of patients responding to treatment.
But what exactly is immunotherapy?