{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:44:45Z","timestamp":1782920685647,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"\n Background &amp; Aims<\/jats:title>\n Iron deficiency anemia (IDA) affects over two billion people, yet up to half of patients show inadequate response to oral iron therapy. We hypothesized that IDA is a primary duodenal mucosal disorder where dysbiosis and immune polarization converge to impair enterocyte iron export. This study integrates mucosal-associated microbiome and transcriptomic profiling to elucidate mechanisms underlying impaired iron handling.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Duodenal biopsies from women with IDA (\n n<\/jats:italic>\n = 11) and matched controls (\n n<\/jats:italic>\n = 9) underwent paired 16S rRNA and RNA-Seq. A Microbial Redox Index (MRI) quantified oxygen-tolerant taxa. Multilayer network modeling linked microbial hubs to epithelial transcriptional remodeling in iron-handling, inflammatory, and barrier-integrity pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n IDA subjects demonstrated expected hematological deficits (hemoglobin 10.02 \u00b1 0.82 vs. 12.69 \u00b1 0.67 g\/dL; ferritin 10.7 [8.2\u201335.3] vs. 49.7 [28.4\u201358.7] ng\/mL;\n P<\/jats:italic>\n &lt; 0.05). Although the overall ratio of oxygen-tolerant to anaerobic taxa was comparable between groups (\n P<\/jats:italic>\n = 0.44), IDA was marked by a collapse of homeostatic ecological control. In controls, Group V a\/V b anaerobes showed a strong inverse correlation with Shannon diversity (\n P<\/jats:italic>\n = 0.009), indicating a stable, niche-restricting anaerobic core. This relationship was lost in IDA, where both oxygen-tolerant and anaerobic taxa displayed positive correlations with Th17 skewed inflammation (IL17A log2FC = +3.59), hypoxic stress (EGLN3 log2FC = +1.31), and sensitized BMP signaling (BMPR2 log2FC = +0.50). These transcriptomic signatures could reflect a functional ferroportin blockade, as reflected by SLC40A1 mRNA upregulation (log2FC = +1.02) concurrent with a proposed model of post translational ferroportin suppression, despite profound cellular iron starvation (TFRC log2FC = +1.58; SLC11A2 log2FC = +2.2). Together, these features are consistent with a possible enterocyte iron retention phenotype. The lncRNA LOC124902620 emerged as a central regulatory hub linking dysbiosis to iron-handling genes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n IDA is a duodenal mucosal disorder where dysbiosis-driven redox shifts and immune activation could support a model of hepcidin associated ferroportin downregulation. This is consistent with a proposed enterocyte iron retention phenotype. Microbial hubs and the LOC124902620 axis are promising targets for precision interventions to restore mucosal iron export.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fnut.2026.1836940","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:50:07Z","timestamp":1782917407000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Duodenal dysbiosis is linked to altered ferroportin related transcriptomics programs in iron deficiency anemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Siwani","family":"Agrawal","sequence":"first","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishikesh","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Jumin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subash Chandra","family":"Samal","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaktiprasad","family":"Mishra","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Autonomous Institute Under Department of Biotechnology, Government of India, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil Kumar","family":"Raghav","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Autonomous Institute Under Department of Biotechnology, Government of India, Bhubaneswar","place":["Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balakrishnan S.","family":"Ramakrishna","sequence":"additional","affiliation":[{"name":"Institute of Gastroenterology, SRM Institutes of Medical Science","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balamurugan","family":"Ramadass","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]},{"name":"Centre of Excellence for Clinical Microbiome and Research (CCMR), All India Institute of Medical Sciences, Bhubaneswar","place":["Odisha, India"]},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide","place":["SA, 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