Redox Signaling in Gut Microbiota Interactions

Summary

Redox signalling in the gastrointestinal tract describes the finely tuned exchange of electrons and reactive species between host tissues and resident microbes. At the mucosal interface, epithelial cells, immune cells and commensal bacteria generate reactive oxygen species (ROS) through dedicated enzymes and metabolic pathways. These ROS act as second messengers to regulate epithelial barrier function, modulate immune responses and shape microbial community structure. In homeostasis, controlled production of hydrogen peroxide and related oxidants reinforces tight junctions and fosters tolerance to beneficial flora. Conversely, excessive or prolonged ROS generation disrupts barrier integrity, provokes inflammatory cascades and promotes dysbiosis. Emerging data reveal that distinct NADPH oxidases within epithelial cells calibrate peroxynitrite formation to limit microbial invasion, while microbial nitrate and nitrite reduction pathways influence local nitric oxide levels, driving shifts in microbial fermentations. Together, these redox circuits underpin host–microbiota symbiosis and, when perturbed, contribute to pathologies ranging from inflammatory bowel disease to colorectal cancer. A deeper understanding of these interwoven pathways offers routes to redox-targeted therapies, precision probiotics and dietary interventions to restore gut health globally.

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Redox Signaling in Gut Microbiota Interactions publication trend

The graph below shows the total number of articles in redox signaling in gut microbiota interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive oxygen-containing molecules that act as signalling mediators or cause oxidative damage.

NADPH oxidase (NOX): A family of membrane-resident enzymes that transfer electrons from NADPH to oxygen, generating superoxide or downstream oxidants.

Dual oxidase 2 (DUOX2): An epithelial NADPH oxidase isoform specialised in hydrogen peroxide production for host defence and signalling.

Peroxynitrite: A potent oxidant formed by the reaction of nitric oxide with superoxide, implicated in barrier disruption and microbial modulation.

Dysbiosis: An imbalance in microbial community composition or function that may disrupt host physiology and promote disease.

References

  1. Dysregulated NOX1-NOS2 activity as hallmark of ileitis in mice. Mucosal Immunology (2024).
  2. Epithelial Dual Oxidase 2 Shapes the Mucosal Microbiome and Contributes to Inflammatory Susceptibility. Antioxidants (2023).
  3. Nitric Oxide Impacts Human Gut Microbiota Diversity and Functionalities. mSystems (2021).

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