By Joe Dangor
A study of the mouse gut microbiome led by researchers from Mayo Clinic may shed light on how cancerous tumors develop and progress in humans. The findings were presented at the 2021 American Association for Cancer Research annual meeting.
"There is growing recognition that healthy tissues accumulate cancer-related mutations over time but they don’t necessarily cause illness," says stem cell and cancer biologist Nagarajan Kannan, Ph.D., who led the study. "We asked the question, what would trigger these aberrant cells to grow uncontrollably and develop into a malignancy?"
Gastroenterologist Purna Kashyap, M.B.B.S., the Bernard and Edith Waterman co-director of the Center for Individualized Medicine Microbiome Program, says the human gut contains large, diverse and self-sustaining microbes that are present in the trillions and contribute to our overall metabolism.
"A bolus of microbes colonizes the gut at birth via transmission from mother to baby and are then constantly shaped by diet and lifestyle," says Dr. Kashyap. “We believe there is great value in understanding how these microbes regulate processes within and outside the gut, to allow us to effectively harness their health benefits."
"In our study we were able to show that oncogenic mammary cells behave differently in animals with and without germs," says Dr. Kannan. "Cancer cells injected into 'bubble mice' (mice that are bred to have no germs) developed into early-onset, highly metastatic tumors," he says. "However, when we injected these cells into regular laboratory mice, they developed into mostly late-onset, benign or poorly metastatic tumors."
Dr. Kannan says he and his colleagues were startled by these observations. They performed additional experiments where they colonized germ-free bubble mice with healthy germs, prepared from feces taken from healthy donor mice. "When these transplanted mice developed into adults, they developed late-onset, 'poorly' metastatic tumors," says Dr. Kannan. "In many ways, the fate of transplanted mice and regular laboratory mice were similar, i.e,, they lived longer without any signs or symptoms of cancer," he says.
The study raises many important questions and challenges current thinking on how tumors develop and progress in humans. There is growing recognition that healthy tissues accumulate cancer-related mutations over time, but they don’t necessarily cause illness.
"What triggers these aberrant cells to grow uncontrollably and develop malignancy is a question we are very interested in," says Dr. Kannan. "Understanding these earliest events in the pathogenesis of cancer may create opportunities for developing new paradigms in cancer prevention, both among individuals and within populations," says Mark Sherman, M.D., a molecular pathologist and epidemiologist at Mayo Clinic.
Dr. Kannan says the findings open a new area of investigation in the pursuit of therapies to prevent and treat cancer. The germ-free bubble mice could play an important role in development of such innovative therapies. "It is important to note that both human and mice guts are colonized by microbes at birth," he says. "Therefore, what is true in mice may also be true in humans, and if that is so, then we may be forced to re-shape our thinking of cancer biology and how we design treatments for cancer."
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