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Chemotherapy, immunity and microbiota—a new triumvirate?

Nature Medicine volume 20, pages 126–127 (2014)Cite this article

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Michael Karin

The gut microbiome affects many physiological processes, and intestinal dysbiosis, in which the microbiome composition is grossly perturbed, is thought to be responsible for a number of pathologies. Two recent Science papers show that the gut microbiome also influences the outcome of cancer therapy by modulating the host inflammatory response1,2. Basically, both papers conclude that an intact microbiome is required for successful tumor control in response to genotoxic as well as immunomodulatory therapies and that tumor-bearing germ-free mice or mice that have been treated with a concoction of antibiotics that eliminate most of the commensal microbiota hardly respond to anticancer therapy. Although the results obtained in mice are clear, it is rather unlikely that most patients with cancer will have a grossly depleted gut microbiome, so it is debatable whether these studies would alter the future practice of cancer treatment. Many genotoxic cancer drugs lead to an inflammatory condition known as mucositis, which is associated with gut barrier deterioration and bacterial translocation. As these drugs also cause neutropenia, bacterial translocation across the gut mucosa can cause severe systemic infections that will require antibiotics. However, antibiotic use in humans rarely leads to nearly complete depletion of the gut microflora, and any dysbiosis that ensues is usually transient. The two papers suggest that the inflammatory response that follows cancer therapy, which is strongly enhanced by the translocating commensals, contributes to tumor eradication through the upregulation of interleukin-17 (IL-17)2 or tumor necrosis factor (TNF)1. So should oncologists make an effort to maintain IL-17 and TNF expression in patients with cancer treated with antibiotics?

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Chemotherapy, immunity and microbiota—a new triumvirate?. Nat Med 20, 126–127 (2014). https://doi.org/10.1038/nm.3473

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