Science Review: Dietary Iron Changes Gut Microbiome and Promotes Secretion of Cancer-Promoting Molecules

Reference:

Liu, C., Gong, J., Zhang, Q., Chen, G., Yin, S., Luo, Z., … He, Z. (2023). Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis. Gut Microbes, 15(1). https://doi.org/10.1080/19490976.2023.2221978

This study was done in mice. Full text here.

This study demonstrates that too much iron in the diet causes gut inflammation and increases gut permeability.

I often remind my patients that a bowl of cheerios has more than 2x as much iron as a steak, and the iron in cereals and other processed foods is inorganic and highly inflammatory.

Key points from the study:

  • Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed.
  • Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake.
  • Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria.
  • Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation.
  • The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway.
  • Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron.
  • Overall, excessive dietary iron perturbs diet – microbiome–epithelium interactions, which contributes to intestinal tumor initiation.

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