The study used quantitative iron measurements to assess how much iron existed in inflamed regions of patients with ulcerative colitis and Crohn’s disease as well as mouse models where gastrointestinal (GI) injury/repair was induced.
When there is iron deficiency, epithelial cells “exhaust iron reserves,” while stem cell compartments still maintain their iron pools. Injury exacerbates this imbalance when it disrupts these compartments and compromises repair.
“Our findings suggest that low levels of dietary iron result in impaired intestinal wound healing as a consequence of compromised proliferation,” the researchers wrote. “In standard diet, epithelial cells and the stem cell compartment maintain adequate iron stores. During injury when the stem cell compartment is disrupted, our data suggest that iron is necessary to restore the regenerative stem cell pool.”
A complicated role
Tissue repair and regeneration gives the body the ability to repair damaged tissues because of trauma, microbial infection or pathological conditions. The researchers noted that this is essential when it comes to the gastrointestinal system “where the rapid turnover of the epithelial layer and continuous exposure to injurious agents necessitate efficient and robust repair mechanisms.”
Following an epithelial injury, epithelial cells “proliferate and migrate to repair the damaged area” and this process serves as a “rapid first response to prevent deeper tissue exposure” to provide a strong barrier against commensal and pathogenic bacteria, the scientists explained.
Iron is now viewed as a key player in regulating cellular metabolism, essential to several biological processes, including hemoglobin formation, oxygen transport, DNA synthesis, mitochondrial respiration and plays a critical role in the immune response.
However, its role proves to be an intricate balance.
“Inflammation is an inherent part of the tissue repair process through the removal of injurious agents and initiation of repair; excessive inflammation can impede healing and result in pathophysiological disease states,” the researchers added. “Iron can induce tissue damage through oxidative stress but is also necessary for anti-inflammatory mechanisms. This results in a complex interaction between iron, inflammation and tissue healing.”
Study details
The researchers used three mouse models of GI injury: a dextran sulfate sodium (DSS) model of colitis, a biopsy wound healing model and an irradiation injury model.
“These models mimic the pathophysiological spectrum of human IBD, post-biopsy repair and radiation trauma, respectively, offering invaluable insights into the functional role of iron in intestinal wound repair,” the researchers noted.
Mice fed a low-iron diet had weakened intestinal wound healing in the three models. The researchers showed that changes in dietary iron intake do not influence the iron content within the stem cell compartment, possessing an adequate iron reservoir to meet their proliferation needs.
However, the scientists wrote that “when an injury disturbs the stem cell compartment, the cells responsible for replenishing this pool require iron to initiate the proliferation process during regeneration.”
Although iron aids in cell proliferation and can resolve inflammation, excessive iron can also cause tissue damage from oxidative stress.
“The role of iron in GI homeostasis is complex and not yet fully understood,” the scientists added. “Our study highlights this and helps to elucidate how iron affects GI tissue repair. A greater understanding of this mechanism may provide targeted therapeutic interventions toward other GI conditions.”
Source: The Journal of Nutrition
doi: doi.org/10.1016/j.tjnut.2024.01.013
“Dietary Iron Is Necessary to Support Proliferative Regeneration after Intestinal Injury”
Authors: Wesley Huang et al.