Bugs and cancer? The plot thickens...

An item from the New York Times gives me the chance to write about two great interests in the same blog piece: bacteria (once a microbiologist, always a microbiologist) and cancer.

Fusobacterium nucleatum, an
accomplice of colorectal cancer

That bacterial infection might cause or promote cancer was debated for most of the 20^th century, but with little solid evidence emerging to support the notions. During the 1980s, Barry Marshall and Robin Warren (the former famously swigging down a flask of culture broth to prove his hypothesis) established that Helicobacter pylori, a common corkscrew-shaped found in the stomach, was an undisputable cause of gastric inflammation and ulcers.

Epidemiological studies involving British, American and Japanese subjects confirmed that H.pylori carriage was indeed associated with an almost four-fold increase in the likelihood of developing gastric cancer and resulted in the WHO designating H.pylori as a Class I carcinogen.

Continuing research has established that the relationship between  H.pylori and cancer is not a simple one of cause and effect,  with H.pylori infection being a factor in some, but not all, forms of stomach cancer and that H.pylori  strains expressing a particular cytotoxin, “CagA”,  are more strongly associated with an elevated risk of cancer than are non-producing strains. Perversely, H.pylori infection appears to be associated with a lower risk of oesophageal cancer.

A more recently uncovered “smoking gun” is the presence of Fusobacterium nucleatum, a common mouth-dweller, found in higher numbers in around half of colorectal tumours than in the surrounding tissue. F.nucleatum- induced inflammation is cited as a plausible contributor to CRC initiation and progression.

But, as with the Helicobacter story, there is no clear-cut cause and effect between infection and cancer. Bacterial species are rarely solitary and the inhabitants of the local milieu or “microbiome” may be more important with respect to cancer initiation and/or progression than the presence of F.nucleatum alone.

CRC may spread to other organs and give rise to tumours in the liver. According to a recent Science publication, if F.nucleatum and its microbiome buddies are present in the original tumour, then they can accompany the metastasizing cancer and pitch up in the liver. CRC dwelling F.nucleatum remained associated with tumours even after their transplantation into mice. Moreover, dosing of tumour-bearing mice with an F.nucleatum-killing antibiotic slowed tumour growth.

Does this make a case for antibiotic therapy or vaccine development to reduce CRC rates? Well, not yet. Antibiotics therapy tends to ablate both the good and bad and, as is hinted at in immuno-oncology studies, certain gut bacteria might positively influence anti-cancer immune responses. And not all F.nucleatum strains might be bad guys. However, it’s feasible that getting a better handle on the mechanism(s) involved in the bacterial promotion of cancer might identify new interventions to improve outcomes or recurrence rates.

Photo credit: CDC Public Image Library

Why is this bacterium hiding in human tumors? Gina Kolata. New York Time online 23^rd November 2017. http://tinyurl.com/ycztnrm4.

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Bullman, S et al. Science 23rd November 2017:eaal5240 DOI: 10.1126/science.aal5240.