“You are what you eat” is more than a catchy aphorism. In cancer treatment response, it is the literal truth: Altering the composition of the gut microbiome can change response to some chemotherapy and immunotherapy regimens, and altering the tumor microbiome can have similar effects on cancer treatments.
“We have known for more than a decade that you can improve treatment effects by manipulating the tumor microbiome,” said Jennifer A. Wargo, MD, MMSc, MD Anderson Cancer Center. “We now know that you can change a checkpoint blockade nonresponder to a responder by altering the gut microbiome.”
Wargo and two other researchers discussed the latest efforts using microbes to promote cancer response on Monday, April 11, during the session Understanding Microbe-Tumor Interactions in Health and Disease: From Basic Mechanisms to Applied Microbial-Based Cancer Therapy. The session can be viewed on the virtual platform by registered meeting participants through July 13, 2022.
Microbes are pervasive in the environment and living organisms, Wargo noted. Humans hold about 20,000 genes and up to 20 million microbial genes. The microbiomes containing those genes are inherently modifiable, and some microbes play active roles in human health and disease.
P-glycoprotein (P-gp) is a primary regulator of the inflammatory diarrhea seen in salmonella infection as well as other pathogenic bacteria, inflammatory bowel disease, lung cancer, Lyme disease-associated arthritis, psoriasis, and other diseases. P-gp also acts as a multidrug efflux transporter that reduces intracellular concentrations of toxic xenobiotics—including chemotherapy agents—contributing to treatment resistance. And the expression of P-gp is modulated by intestinal microbiota.
“Bacteria make the best scientists,” said session chair Beth McCormick, PhD, University of Massachusetts Chan School of Medicine.
Loss of P-gp is associated with intestinal inflammation, she explained. Some taxa are associated with increased expression of the protein by generating short-chain fatty acids and secondary bile acids from the fermentation of dietary fiber, contributing to homeostasis.
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