Table 1.

Areas necessitating further investigation to improve the diagnostic and therapeutic processes for iron deficiency in patients with Inflammatory Bowel Disease.

Area		Rationale
Iron metabolism	Hepcidin regulation Ferroportin regulation Heme iron uptake Intracellular iron regulation Iron absorption regulation by host-microbiota interactions	Much is still unknown about iron metabolism, including the factors that regulate key proteins and their expression, function, or even the role of other organs, e.g., the pancreas. Establishing regulatory pathways will help understand the relationship between iron status and disease.
Physiology	ID classification by different stages and severity Effect of iron status on different physiological functions, e.g., immune system Association between iron status, hypoxia, and oxidative stress Association between iron status and the intestinal microbiota Association between iron status and other deficiencies, e.g., zinc	There are no definitions of mild, moderate, or severe ID. Establishing different phases of ID and its relation to various physiological processes will help to improve the diagnostic and therapeutic processes. In addition, the effect of hypoxia on iron deficiency and oxidative stress should be explored further, given their frequent co-existence in patients with IBD.
Diagnosis	Assessing systemic iron status Diagnostic biomarker standardization Assessing abnormalities in iron metabolism	Currently used biomarkers are susceptible to inflammation, which impacts the diagnostic accuracy and the utility of a common cut-off point. The discovery and validation of new diagnostic biomarkers and their quantification methods will help identify patients needing treatment in an accurate and timely manner. Currently, assessment of congenital abnormalities regarding iron status is limited; understanding and diagnosing abnormallities in iron metabolism will aid prescribing the appropriate therapy.
Therapy	Appropriate nutrition Optimizing iron therapy Predicting response to iron therapy	More research is needed to establish guidelines for appropriate nutrition to optimize iron status in patients with co-morbidities, a history of abdominal surgery, use of medications (e.g., PPIs), and active IBD. Improving oral and intravenous iron therapy is necessary to ensure therapeutic compliance, ID recurrence prevention, and optimization of clinical outcomes.

ID: iron deficiency, IBD: Inflammatory Bowel Disease, PPI: proton-pump inhibitor.