Study Links Gut Bacteria with Chemoresistance to Colorectal Cancer

Bacterium may hold the key to preventing resistance to chemotherapy.

A specific gut bacteria is associated with cancer recurrence and poor outcomes in patients with colorectal cancer, new findings indicate.

Fusobacterium nucleatum is a heterogeneous oral pathogen that also commonly resides in the human gut mucosa. In prior research, gut microbiota has been linked to chronic inflammation and carcinogens.

In a study published in Cell, investigators sought to examine whether gut microbiota contributes to chemotherapy resistance in patients with colorectal cancer, the second leading cause of cancer-related death worldwide.

“We treat patients with chemotherapy so that it will ultimately induce tumor cell apoptosis,” said author Weiping Zou, MD, PhD. “But some cancer cells have a way to avoid apoptosis that is induced by chemotherapy. Those cells escape from the apoptosis process by activating a cell-survival mechanism called autophagy. That mechanism protects cancer cells from destructing.

“Once autophagy is active, the cancer becomes resistant to chemotherapy. Then Fusobacterium nucleatum keeps autophagy turned on. That’s how the tumor cells may be able to avoid the induced apoptosis.”

Although autophagy can normally be switched on or off, F. nucleatum prevents the expression of 2 microRNAs preventing autophagy from switching off, according to the authors.

Prior studies have shown that adaptive immunity is reversely associated with resistance of cisplatin. Based on these findings, the investigators sought to determine whether bacterium-mediated innate immune signaling regulates chemotherapy resistance in colon cancer.

The innate immune system refers to the cells and molecular mechanisms that attack pathogens, whereas the adaptive immune system refers to the body’s response to specific antigens.

“We knew that the body uses both systems, adaptive and innate, to fight cancer and infectious pathogens,” Dr Zou said. “That gave us the inspiration to look further at bacterium associated with innate immune signaling.

“The results of the research were a surprise. We did not expect the bacterium to contribute to chemoresistance.”

Despite these findings there are still several other questions regarding F. nucleatum that remains unanswered, the authors noted. This includes what would happen if the bacterium was reduced or blocked, and whether other prevalent bacterium creates a similar issue with chemotherapy resistance.

“Right now, we don’t have a specific approach to selectively treat or control Fusobacterium nucleatum,” Dr Zou said. “Also, we don’t know if an abundance of this bacterium is found in any other types of cancer chemoresistance. Still, based on our studies, we think that if we deal with this bacterium, we may be able to delay and prevent chemoresistance in colorectal cancer.”