The double face of bacteria: promoters of cancer and our allies to fight it

The role of microbes in the formation, diagnosis, prognosis, and treatment of cancer has been debated for decades. In fact, this link began to be established quite some time ago, in 1868, when the German physician William Busch observed spontaneous tumor regressions in patients infected with the bacterium. Streptococcus pyogenes.

Shortly thereafter, the American surgeon and oncologist William Coley tested a vaccine designed with species of streptococcus Y Serratia in patients with terminal cancer, demonstrating a disease-free survival of more than 10 years in approximately 30% of them. It represents the first demonstration of what has been called immunotherapy.

Since then, advances in microorganism and cancer research have advanced stratospherically, and our understanding of immuno-oncology has fueled new diagnostic and therapeutic approaches.

Directly responsible…

The microbiota or set of microbes associated with a tumor is an intrinsic component of the ecosystem cells, molecules and blood vessels that surround it (the so-called microenvironment). Their genetic variety may provide an opportunity to improve the diagnosis and prognosis of the disease.

However, of the more than a thousand different microbial species, only 11 are labeled as human carcinogens or oncomicrobes by the International Association of Cancer Registries. These oncomicrobials cause approximately 2.2 million cases per year, around 13% of all those registered in the world. It is the case of Streptococcus bovis wave Morganella morganii, associated with colon cancer; the Chlamydia pneumoniae, with the lung; or the Helicobacter pyloriresponsible for gastric cancer.

… and necessary accomplices

Another additional category, that of microorganisms partners in crimeenhances the transformation of normal cells into cancer cells, but they are not directly responsible for this process.

Inside the tumor, microorganisms are distributed in neighborhoods called microniches, which are less vascularized and weaken the immune reaction. These microbial communities vary by cancer type, and specific bacteria may contribute to the onset and development of the disease and compromise response to treatment.

A recent study has drawn the first atlas of fungi, bacteria, and immune cells in tumors after characterizing 17,401 tissue, blood, and plasma samples from patients with 35 types of cancer. This work broadens the panorama of the microbiome of the disease, although it does not establish a cause-effect relationship. What it does do is improve the ability to diagnose and offer a prognosis in tumors –even at an early stage and without prior treatment– based on the analysis of tissue and plasma bacteria.

The researchers have also found differences in genomic alterations of tumor DNA circulating outside of cells between samples from healthy individuals and patients with multiple types of blood cancers. This potential cancer diagnostic tool deserves further exploration.

How can gut bacteria help?

Human beings can be considered as a metaorganism: 57% of our cells and up to 99% of our genes are microbial. The vast majority come from intestinal bacteria, which play a fundamental role in the development of cancer, but can also stop it. Let’s see how.

Cancer can arise when the intestinal mucosal barriers are broken. Thus, the deviation of the bacteria or their metabolites (the products of cellular metabolism) generate inflammation and attenuate the reaction of our defenses in tumor microenvironments.

Many of the pathways that mediate this interaction involve not only cytokines, proteins that generate inflammation, but also the aforementioned metabolites. These can cause tumor mutations and modulate the action of immune checkpoint inhibitors.

Thus, it has been shown that radiotherapy is more effective when an antibiotic called vancomycin eliminates certain metabolites from bacteria. Clostridials. On the contrary, experts have observed that other types of metabolites – tryptophan and propionate – derived from intestinal microbes provide long-term radioprotection.

Furthermore, an intact gut microbiome, as opposed to one altered by antibiotics, is necessary to prevent leukemia progression in genetically predisposed mice.

Verifying these effects of the microbiota has revitalized efforts to change its composition as a form of immunotherapy. However, and despite the extensive scientific evidence, no treatment has yet been marketed.

therapeutic opportunities

Gut microbes are intimately involved in the biotransformation of drugs, with unintended consequences for cancer control. Antibiotics appear to override the immunotherapy response by inhibiting the gut microbiome. This interaction between microorganisms and drugs deserves further study.

Given the role that bacteria play in the evolution of cancer, dietary changes should be promoted in treatments, as well as the administration of prebiotics (molecules that promote the growth of beneficial microbes), probiotics, postbiotics (molecules derived from microbes) and antibiotics. . Modified bacteria could even be injected into the interior of the tumor.

Other tools within our reach are fecal microbiota transplantation or the use of commercial probiotics.

In the latter case, few commercial formulations have yet been tested to determine their impact; some of them even favor the formation of tumors or cause bacteremia (invasion of bacteria in the bloodstream) in critically ill patients. Therefore, the indiscriminate administration of probiotics to patients is inadvisable.

In short, understanding how we can modulate the microbiota is crucial to guide clinical applications and increase the therapeutic arsenal against cancer.

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