Diet and gut microbiome interactions in gynecologic cancer.

Over the last decade, there has been a dramatic surge in research exploring the human gut microbiome and its role in health and disease. It is now widely accepted that commensal microorganisms coexist within the human gastrointestinal tract and other organs, including those of the reproductive tract. These microorganisms, which are collectively known as the "microbiome", contribute to maintaining host physiology and to the development of pathology. Next generation sequencing and multi-'omics' technology has enriched our understanding of the complex and interdependent relationship that exists between the host and microbiome. Global changes in the microbiome are known to be influenced by dietary, genetic, lifestyle, and environmental factors. Accumulating data have shown that alterations in the gut microbiome contribute to the development, prognosis and treatment of many disease states including cancer primarily through interactions with the immune system. However, there are large gaps in knowledge regarding the association between the gut microbiome and gynecologic cancers, and research characterizing the reproductive tract microbiome is insufficient. Herein, we explore the mechanisms by which alterations in the gut and reproductive tract microbiome contribute to carcinogenesis focusing on obesity, hyperestrogenism, inflammation and altered tumor metabolism. The impact of the gut microbiome on response to anti-cancer therapy is highlighted with an emphasis on immune checkpoint inhibitor efficacy in gynecologic cancers. We discuss dietary interventions that are likely to modulate the metabolic and immunologic milieu as well as tumor microenvironment through the gut microbiome including intermittent fasting/ketogenic diet, high fiber diet, use of probiotics and the metabolic management of obesity. We conclude that enhanced understanding of the microbiome in gynecologic cancers coupled with thorough evaluation of metabolic and metagenomic analyses would enable us to integrate novel preventative strategies and adjunctive interventions into the care of women with gynecologic cancers.