{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:09:25Z","timestamp":1789427365979,"version":"build-2803163510"},"reference-count":385,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Nutritional immunity is a major facet of host defense, wherein the host immune system strategically limits pathogen access to critical nutrients, including iron, zinc, vitamins, lipids, and amino acids, to repress microbial proliferation and virulence. This review provides a comprehensive synthesis of the molecular mechanisms that power nutrient immunity, including metal homeostasis, nutrient competition, transporter modulation, hormonal regulation, and direct antimicrobial actions. We examine nutrient-specific strategies employed by the host, such as iron-withholding mechanisms, vitamin deprivation, and copper-mediated toxicity. We also explore how diverse pathogens, including extracellular, intracellular, and eukaryotic pathogens, adapt to these hostile nutritional landscapes through siderophore diversification, regulatory integration, and metabolic rewiring. Comparative genomic analyses reveal convergent evolution in nutrient acquisition systems, illuminating the dynamic arms race between host restriction and microbial evasion. We examine the immunological mechanisms that regulate nutritional immunity. Further, we discuss the translational potential of nutritional immunity, cutting across nutrient-based therapies, host-directed interventions, and emerging diagnostic biomarkers. Finally, we suggest future directions that synergize nutritional immunity with microbiome ecology, global malnutrition, and personalized medicine. By elucidating the interconnection between metabolism and immunity, this review highlights the therapeutic promise of starving or toxifying the pathogen to save the host.<\/jats:p>","DOI":"10.3390\/pathogens15020176","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:13:01Z","timestamp":1770289981000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms and Therapeutic Potential of Nutritional Immunity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6559-7176","authenticated-orcid":false,"given":"Charles Egede","family":"Ugwu","sequence":"first","affiliation":[{"name":"Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-3638","authenticated-orcid":false,"given":"Olalekan Chris","family":"Akinsulie","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyin Florence","family":"Ayandokun","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Favour Akinfemi","family":"Ajibade","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3923-8414","authenticated-orcid":false,"given":"Sammuel","family":"Shahzad","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2610-4600","authenticated-orcid":false,"given":"Victor Ayodele","family":"Aliyu","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0300-1474","authenticated-orcid":false,"given":"Moyinoluwa Joshua","family":"Oladoye","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Idris","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingsley Ogochukwu","family":"Obasi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Wolverhampton, Wolverhampton WV1 1LY, West Midlands, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel Kosisochukwu","family":"Edeh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al-Amin Adebare","family":"Olojede","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Ibadan, Ibadan 200001, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1616-7848","authenticated-orcid":false,"given":"Chizaram Blessing","family":"Ukauwa","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Abuja, Abuja 902101, Federal Capital Territory, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ipoola","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Bergen, 5007 Bergen, Vestland County, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity Chinonso","family":"Ugwu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420110, Anambra State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Chizobam","family":"Ugorji","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Imo State University, Owerri 460108, Imo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s41256-023-00319-w","article-title":"Infectious disease control: From health security strengthening to health systems improvement at global level","volume":"8","author":"Zhang","year":"2023","journal-title":"Glob. 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