# The interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease

## TL;DR

This paper explores how gut microbiota and a type of cell death called ferroptosis interact to worsen inflammatory bowel disease, offering new insights for potential treatments.

## Contribution

The paper introduces the concept of the microbiota–ferroptosis axis in IBD pathogenesis and highlights novel therapeutic strategies targeting this interaction.

## Key findings

- Dysregulated ferroptosis, influenced by gut microbiota, worsens microbial imbalance in IBD.
- Gut microbiota affects IBD through metabolite regulation, immune homeostasis, and intestinal barrier protection.
- Targeting ferroptosis inhibition and microbiota interventions may improve clinical outcomes in IBD.

## Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing disorder driven by complex interactions between genetic susceptibility, immune dysregulation, and environmental factors. Ferroptosis has been identified as a key regulator in the progression of IBD. While much research focuses on endogenous signaling pathways, extrinsic mechanisms—particularly the modulation of IBD through the gut microbiota-induced ferroptosis remain underexplored. Dysregulated ferroptosis, influenced by gut microbiota, exacerbates microbial imbalance, creating a vicious cycle. Notably, the gut microbiota plays a critical role in IBD progression through multidimensional mechanisms, including regulation of metabolites, maintenance of immune homeostasis, and protection of the intestinal barrier. This review examines the microbiota–ferroptosis axis in IBD pathogenesis, aiming to provide insights into potential therapeutic strategies. In particular, we discuss emerging treatments targeting ferroptosis inhibition, iron homeostasis regulation, and microbiota interventions, which hold promise for improving clinical outcomes and promoting pathological recovery in IBD patients.

Schematic illustration of the interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease.Diagram illustrating the interrelationships in Inflammatory Bowel Disease (IBD). Gut microbiota imbalance, with decreased probiotic and increased pathogenic bacteria, impacts metabolism and iron overload. This triggers lipid ROS and ferroptosis, aggravating intestinal dysbacteriosis and iron metabolism disorder. These processes contribute to barrier dysfunction in the intestinal epithelium, affecting tight junction proteins like Zo-1 and Occludin, and increasing inflammatory markers TNF-alpha, IL1-beta, and IL-17. Arrows indicate the flow and interactions between elements.

Schematic illustration of the interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease.