Disrupted coupling between ferritin and iron absorption in enteropathy-related anemia: Evidence for a dual-pathway model

doi:10.3748/wjg.119263

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Aug 21, 2026; 32(31): 119263
Published online Aug 21, 2026. doi: 10.3748/wjg.119263

Disrupted coupling between ferritin and iron absorption in enteropathy-related anemia: Evidence for a dual-pathway model

Olesja Basina, Jelena Derova, Nikola Krumina, Maksims Zolovs, Sandra Lejniece, Aleksejs Derovs

Olesja Basina, Aleksejs Derovs, VCA Gastroenterology and Endoscopy Department, VCA, Riga LV1035, Riga, Latvia

Olesja Basina, Jelena Derova, Nikola Krumina, Sandra Lejniece, Aleksejs Derovs, Department of Internal Diseases, Riga Stradins University, Riga LV1007, Riga, Latvia

Olesja Basina, Aleksejs Derovs, Outpatient Department Unit, Riga East University Hospital, Riga LV1038, Riga, Latvia

Jelena Derova, Aleksejs Derovs, Department of Gastroenterology, Latvian Maritime Medicine Centre, Riga LV1005, Riga, Latvia

Jelena Derova, Aleksejs Derovs, Digestive Disease Society of Latvia, Jurmala LV2010, Jurmala, Latvia

Maksims Zolovs, Statistics Unit of RSU Faculty of Medicine, Riga Stradins University, Riga LV1007, Riga, Latvia

Maksims Zolovs, Institute of Life Sciences and Technology, Daugavpils University, Daugavpils LV5401, Augsdaugava, Latvia

Sandra Lejniece, Hematology Clinic, Riga East University Hospital, Riga LV1038, Riga, Latvia

Author contributions: Lejniece S and Derovs A designed the research study; Basina O and Derova J performed the research; Basina O, Derova J, and Derovs A contributed clinical data; Basina O and Zolovs M analyzed the data; Basina O and Krumina N wrote the manuscript; Derovs A revised the manuscript. All authors have read and approved the final manuscript.

AI contribution statement: ChatGPT was used for language editing of selected passages in the Introduction and Discussion. No part of the manuscript was AI-generated. The study concept, design, data collection, statistical analysis, and all scientific conclusions are the work of the authors. AI use was limited to language editing only. No AI tool was involved in study design or interpretation of results. No images were AI-generated. The authors also note that AI screening was not performed at submission or during peer review - the stages where such checks are standard practice in other journals. Raising this issue at the production stage, after formal acceptance, is procedurally irregular. AI detection tools produce false positives, and this is especially common in manuscripts written in rigorous academic English by experienced researchers.

Institutional review board statement: The study was approved by the Riga East University Hospital Support Foundation Medical and Biomedical Research Ethics Committee (protocol No. 10-A/14) and conducted in accordance with the Declaration of Helsinki.

Informed consent statement: All involved persons (subjects) gave their written informed consent prior to study inclusion.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. Article processing charge support from Riga Stradins University no direct personal payment to the author.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author upon reasonable request at olesja.basina@rsu.lv. Participants consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.

Corresponding author: Olesja Basina, MD, Chief Physician, Doctorate Student, Lecturer, VCA Gastroenterology and Endoscopy Department, VCA, Nicgales Street 5, Riga LV1035, Riga, Latvia. olesja.basina@rsu.lv

Received: January 26, 2026
Revised: March 13, 2026
Accepted: April 22, 2026
Published online: August 21, 2026
Processing time: 190 Days and 19.8 Hours

Abstract

BACKGROUND

Serum ferritin is widely used as a biomarker of iron deficiency; however, its diagnostic value in patients with enteropathy remains uncertain, particularly in the absence of overt bleeding or systemic inflammation. As both a storage protein and an acute-phase reactant, ferritin may not accurately reflect functional iron availability in the presence of small-bowel mucosal pathology. Enteropathies affecting absorptive enterocytes can impair intestinal iron uptake through structural and regulatory mechanisms that are not captured by conventional biomarkers alone. Video capsule endoscopy offers a non-invasive approach to assessing mucosal integrity, yet its relationship with biochemical indices of iron absorption remains poorly explored.

AIM

To evaluate relationships among serum ferritin, intestinal iron absorption, and enteropathy-related mucosal changes in unexplained anemia.

METHODS

In this single-center prospective study, patients with unexplained anemia or fatigue underwent video capsule endoscopy and a 4-hour oral iron absorption test (ΔFe), and completed the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire. Pathway analysis based on structural equation modeling principles, together with general linear models, was used to evaluate associations among mucosal injury, iron absorption, iron biomarkers, and functional status.

RESULTS

The analysis supported a dual-pathway model, in which enteropathy independently influenced both intestinal iron absorption (ΔFe, P = 0.005) and serum ferritin levels (P = 0.002). ΔFe did not significantly predict serum ferritin levels (P = 0.619), indicating an interruption of a simple serial absorption pathway. Patients with lower ΔFe demonstrated a trend toward lower FACIT-Fatigue scores, indicating worse fatigue; however, this difference did not reach statistical significance. FACIT-Fatigue scores showed a weak but significant correlation with serum ferritin (r = 0.310, P = 0.021) but not with short-term iron absorption (ΔFe, P = 0.412).

CONCLUSION

Enteropathy independently impairs iron absorption and alters ferritin levels through dissociated pathways. Combined use of capsule endoscopy and oral iron absorption testing may improve diagnostic evaluation of unexplained anemia.

Keywords: Iron deficiency; Enteropathy; Ferritin; Capsule endoscopy; Iron absorption; Fatigue; Functional Assessment of Chronic Illness Therapy; Pathway modeling

Core Tip: Iron deficiency anemia without overt gastrointestinal bleeding remains a diagnostic challenge, particularly in patients with suspected small-bowel disease. In this study, we integrated video capsule endoscopy findings with an oral iron absorption test, serum iron biomarkers, and fatigue scores. Our results demonstrate that enteropathy independently impairs intestinal iron absorption and alters ferritin levels, yet without a direct association between these two processes. This dissociation suggests that ferritin alone may not accurately reflect functional iron deficiency in enteropathy and highlights the importance of assessing small-bowel mucosal integrity in patients with unexplained anemia or fatigue.