REVIEW article

Front. Cell. Infect. Microbiol.

Sec. Microbes and Innate Immunity

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1532255

"NO: A Key Player in Microbiome Dynamics and Cancer Pathogenesis"

Provisionally accepted
Zhila  IzadiZhila Izadi1*Seyedeh  Kimia JasemiSeyedeh Kimia Jasemi2Hossein  FaridafsharHossein Faridafshar2Mohammed  Namiq AminMohammed Namiq Amin2Mehregan  BabamohamadiMehregan Babamohamadi3Marjan  FalahatiMarjan Falahati2Roshanak  AmirianRoshanak Amirian2
  • 1Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
  • 2Kermanshah University of Medical Sciences, Kermanshah, Kerman, Iran
  • 3University of Tabriz, Tabriz, East Azerbaijan, Iran

The final, formatted version of the article will be published soon.

The human microbiome refers to the genomic content of microorganisms inhabiting the human body, including the lungs, oral cavity, intestinal tract, esophagus, and other areas. The human oral microbiota is a diverse and complex ecosystem that includes bacteria, microeukaryotes, archaea, and viruses. These communities have a highly structured biogeography resulting from the various microenvironments in the oral cavity, shaping local metabolic exchange. Dietary nitrate (NO3 -) is an ion naturally present in vegetables, especially leafy greens. When consumed, it leads to the production of nitric oxide (NO). This bioactive molecule benefits bodily functions like host defense and neuronal communication and improves vascular and metabolic health. Dietary NO3is reduced to NO via the nitrate-nitrite-NO pathway, facilitated by nitrate-reducing bacteria inside the oral cavity. NO has a leading role in different types of diseases, including cancer, cardiovascular disease, and diabetes. The bioavailability of NO is greatly enhanced by the activity of bacteria residing in the mouth, which reduces NO₃⁻to NO2 -and increases the concentration of circulating NO2 -. NO is the key to causing different malignancies, including gastrointestinal cancers. NO can cause cell death by inducing DNA damage and anti-apoptotic signaling pathways.Low to moderate levels of NO derived from tumors can activate angiogenesis and promote an invasive phenotype, while high levels of NO may have an anti-tumor effect in protecting against cancer.In this review, we intend to discuss the human microbiome, dietary NO₃⁻consumption, the vital role of NO in the human body, types of cancers, and treatments based on it.

Keywords: Nitric Oxide, Dietary nitrate, Nitrite (NO2 -), Nitrate (NO3 -), oral microbiome, microbiota, Gastrointestinal cancers, iNOS

Received: 21 Nov 2024; Accepted: 29 May 2025.

Copyright: © 2025 Izadi, Jasemi, Faridafshar, Namiq Amin, Babamohamadi, Falahati and Amirian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zhila Izadi, Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

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