Genetically engineered probiotics to turn vegetables into cancer-killing agents


Imagine recruiting a strain of gut bacteria to help target and kill cancer cells in your colon? A team from the National University of Singapore (NUS) is doing exactly that – genetically modifying a common type of gut bacteria so it locks onto colorectal cancer cells and turns a substance found in broccoli into a cancer-killing toxin.

This remarkable research starts with genetically modifying a harmless form of bacteria commonly found in our gut called E. coli Nissle. The bacteria is engineered to bind to a compound called heparan sulphate proteoglycan, which is found on the surface of colorectal cancer cells.

The microbe lands on the cancer cells and then sits waiting for its host to consume a foodstuff containing glucosinolates. Found in broccoli, cabbage and other cruciferous vegetables, the glucosinolates are converted into a molecule called sulphoraphane – a known cancer-killing compound – via an enzyme secreted from the engineered bacteria.

The study first tested the process in vitro and found the combination of engineered bacteria and glucosinolates killed over 95 percent of colorectal cancer cells. Moving to mouse models the results were equally impressive, reducing tumor numbers by a striking 75 percent.

There are of course plenty of hurdles to overcome before this kind of research is ever practically implemented in human beings. Not the least of which are questions over the unintended side effects of seeding a human subject with genetically engineered bacteria. There are teams currently working on producing a “fail-safe” system for genetically engineered bacteria, similar to a kind of kill-switch, in case the bacteria start behaving in an unintended way.

The NUS team sees a future where these engineered bacteria are consumed as probiotics either to prevent cancer, or to kill lingering tumor cells that were too small to be identified during a surgical removal. Eating your broccoli could literally become a medical necessity.

“One exciting aspect of our strategy is that it just capitalizes on our lifestyle, potentially transforming our normal diet into a sustainable, low-cost therapeutic regimen,” says Matthew Chang, one of the researchers on the project.

The research was published in the journal Nature Biomedical Engineering.

Source: National University of Singapore via ScienceDaily


Scientists: Lack of Good Gut Bacteria Could Be Giving You Cancer



Could cancer really be a bacteria-related disease?


For many years now it has been widely known that smoking, certain dietary factors, obesity, and many other factors are major contributors to cancer incidence. However, a growing body of research has shown that specific changes in the intestinal flora, or dysbiosis, can be found in the stools or on the colonic walls of patients with diseases such as colon cancer.

This has led to hypotheses suggesting that cancers such as colon cancer are in fact bacteria-related diseases, with some species being referred to as “drivers,” and others “promoters.”

“Thus, it appears that microbiota may be considered a platform offering host and environment interactions for studying CRCs. The hypothesis that colon cancer might be a bacteria-related disease is suggested and perspectives are discussed.”
Although most of the aforementioned studies did not state whether the dysbiosis found in colon cancer patients was a cause or consequence of the disease, quantification of major bacterial groups allowed an identification of the Bacteroidetes family as predominant (present as the most influential main factor) in colon cancer.

In fact, the common intestinal commensal known as Bacteroidetes fragilis has been found to induce spontaneous colon cancer in mice bred to mimic familial polyposis in humans. Generally, lower numbers of tumors are seen in mice that are “germ-free” than in those with “conventional” (but not necessarily healthy) gut flora, regardless of whatever carcinogens or mutations are used to induce cancers.

In addition to this, Fusobacterium nucleatum is associated with both gum disease, as it is a key component of periodontal plaque, and colorectal cancer; however it may only be a promoting cofactor. The phyla known as Firmicutes (62%), Bacteroidetes (26%) and Proteobacteria (11%) are the most dominant of bacteria found adhered to precancerous polyps.

Mechanisms of carcinogenesis caused by colonic bacteria include bacteria-induced DNA alteration, which may be caused by E. coli and Enterococcus faecalis; bacterial enzyme activity, which can activate carcinogens or make them more potent; and chronic inflammation.

However, Lactobacillus and Bifidobacterium species of bacteria, found in the vast majority of commercial probiotics, can reduce this inflammation, protect against DNA damage, and inhibit carcinogen activating enzymes. On top of this, fermentation of dietary fibre by beneficial species of bacteria produces short chain fatty acids, which protect against tumor formation.

A Link Between Internal Bacterial Imbalance and Breast Cancer

Another study has also found a possible link between dysbiosis and breast cancer. For the research, the breast microbiota from tumor tissue and paired normal adjacent tissue was analysed from 20 patients. Half of the taxonomic units that were more abundant in normal tissue belonged to the genus Sphingomonas, while two of the three more abundant in tumor tissue belonged to the Methylobacterium genus. This was because Sphingomonas was not present in tumors.

However, dysbiosis found in this study may be due to a downregulation of antibacterial genes in tumors, but the decrease in expression of these genes due to other environmental factors may still be a cause of tumor formation. Dysbiosis found in areas outside of the intestine is also likely to indicate insufficient immune function or even leaky gut syndrome, as it is entirely possible that certain bacteria are able to influence the expression of a cell’s antibacterial genes in order to ensure their own survival.

Another Gut Microbiome-Cancer Connection

In addition to breast and colon cancer, chronic Salmonella enterica infection has been associated with gallbladder cancer; while Chlamydia pneumonia, Haemophilus influenza, and Candida albicans have been linked with lung cancer.

It is also widely known that untreated Helicobacter pylori can result in stomach cancer.

Yet another mechanism behind dysbiosis-driven cancers is the activation of Pathogen Recognition Receptors, which is caused by dysbiosis. In fact, mice lacking the PRR known as TLR-4 have a reduced risk of colon, liver, skin, and pancreatic cancers. This is because of an increase in free radicals and subsequent inflammation and DNA damage.

However, all of these findings demonstrate the importance of not only anti-cancer species of bacteria, but also a strong immune system in general, just as cancers “caused” by a virus such as HPV are prevented by the immune system’s ability to quickly clear the infection.

Once again, gut health and internal flora prove to be absolute key factors in determining our overall health and chance of developing disease.


Microferm wordt als probiotica gebruikt om de darmflora te optimaliseren.