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Nutrients
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Impacts of Micronutrients on Immune System and Inflammatory Diseases
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Impacts of Micronutrients on Immune System and Inflammatory Diseases

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Immunology".

Deadline for manuscript submissions: closed (5 January 2025) | Viewed by 11513

Special Issue Editor

Dr. Renata Ramalho

E-Mail Website
Guest Editor
Egas Moniz School of Health and Science, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal
Interests: nutritional immunology; clinical immunology; tumor immunology; precision nutrition; immunosenescence & immunometabolism

Special Issue Information

Dear Colleagues,

The hallmark of nutritional immunology as a discipline has been the recognition that almost any specific and sufficiently severe nutritional deficiency can interfere with immunological functions. Nutrition and immunology have a multi-level synergistic interaction that has been described as «Nutrition and the 4 “Is”» — infection, immunity, inflammation, and injury. This emphasises that the relationship in question transcends the mere observation that malnourished individuals are at a heightened risk of contracting infections; it also encompasses the understanding that immune cells and other immune system components are impacted by micronutrients deficiencies, and that adequate nutrition not only sustains immune cells but also influences their metabolism. The impact of amino-acids, fatty acids, vitamins, and minerals on immune cells, in terms of their physiology and development, is significant and should be considered while treating a patient. Emerging global issues such as stressors, cancer, overnutrition, chronic diseases, infections and ageing are reshaping nutritional immunology research, thereby paving the way for innovative pathways that seek to improve nutrition, enhance immune function, and provide "better" healthcare.

This Special Issue aims to present manuscripts that fall within the broad scope of nutritional immunology, from molecular to clinical aspects, and that contribute to strengthening this area of knowledge. We welcome submissions of original research articles, case reports, reviews and mini-reviews.

Dr. Renata Ramalho
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aging
  • arginine
  • cachexia
  • caloric restriction
  • cancer
  • cardiovascular diseases
  • complement system
  • COVID-19
  • cytokines
  • diabetes
  • diet
  • dietary patterns
  • glutamine
  • immune cells
  • immunity
  • immunometabolism
  • infection
  • inflammation
  • injury
  • malnutrition
  • metabolic pathways
  • metabolism
  • microbiome
  • minerals
  • muscle mass
  • nutrition
  • obesity
  • omega 3
  • oxidative stress
  • SARS-Cov-2
  • senescence
  • vitamins

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Editorial

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4 pages, 154 KiB  
Editorial
Thinking Beyond Food to Nutrition and Beyond Cells to Immunology
by Renata Ramalho
Nutrients 2025, 17(7), 1254; https://doi.org/10.3390/nu17071254 - 3 Apr 2025
Viewed by 288
Abstract
By the time I was tasked to lead a Special Issue on the “Impacts of Micronutrients on Immune System and Inflammatory Diseases”, seeing publications from so many different areas was something I could not have expected [...] Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)

Research

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17 pages, 1743 KiB  
Article
The Immunomodulatory Activity of High Doses of Vitamin D in Critical Care Patients with Severe SARS-CoV-2 Pneumonia—A Randomized Controlled Trial
by Ana Moura Gonçalves, Sónia Velho, Bárbara Rodrigues, Maria Lobo Antunes, Miguel Cardoso, Ana Godinho-Santos, João Gonçalves and António Marinho
Nutrients 2025, 17(3), 540; https://doi.org/10.3390/nu17030540 - 31 Jan 2025
Viewed by 1456
Abstract
Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. [...] Read more.
Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. Methods: A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes’ VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. Results: The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [p = 0.002] and seventh [p < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes’ VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. Conclusion: Supplementation with higher doses of cholecalciferol may contribute to a significant increase in 25vitD levels but not in LL37 levels. Higher LL37 levels on admission may be related to a decrease in ICU, hospital, and 60-day mortality. VDR gene expression in monocytes is much higher in patients supplemented with higher doses of cholecalciferol. Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)
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12 pages, 1478 KiB  
Article
Anti-Inflammatory Activity of the Combination of Nobiletin and Docosahexaenoic Acid in Lipopolysaccharide-Stimulated RAW 264.7 Cells: A Potential Synergistic Anti-Inflammatory Effect
by Kosuke Nishi, Yuki Nakatani, Momoko Ishida, Ayumu Kadota and Takuya Sugahara
Nutrients 2024, 16(13), 2080; https://doi.org/10.3390/nu16132080 - 29 Jun 2024
Cited by 2 | Viewed by 1967
Abstract
This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) [...] Read more.
This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-κB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination. Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)
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Review

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11 pages, 574 KiB  
Review
The Role of Breast Milk Cell-Free DNA in the Regulation of the Neonatal Immune Response
by Tamim Rezai, Shani Fell-Hakai, Shalini Guleria and Gergely Toldi
Nutrients 2024, 16(24), 4373; https://doi.org/10.3390/nu16244373 - 19 Dec 2024
Cited by 2 | Viewed by 1094
Abstract
The neonatal period is a critical phase for the development of the intestinal immune system, marked by rapid adaptation to the external environment and unique nutritional demands. Breast milk plays a pivotal role in this transition, yet the mechanisms by which it influences [...] Read more.
The neonatal period is a critical phase for the development of the intestinal immune system, marked by rapid adaptation to the external environment and unique nutritional demands. Breast milk plays a pivotal role in this transition, yet the mechanisms by which it influences neonatal mucosal immunity remain unclear. This review examines the potential mechanisms by which cell-free DNA (cfDNA) in breast milk may impact neonatal immune development, particularly through Toll-like receptor 9 (TLR9) signalling and gut microbiota interactions. We propose that cfDNA in breast milk interacts with TLR9 on the apical surface of neonatal intestinal epithelial cells, potentially serving as an initial anti-inflammatory stimulus before the establishment of commensal bacteria. This hypothesis is supported by the high concentration and stability of cfDNA in breast milk, as well as the known activation of TLR9 by mitochondrial DNA in breast milk. The review emphasises the need for further empirical research to validate these interactions and their implications for neonatal health, suggesting that understanding these dynamics could lead to improved strategies for neonatal care and disease prevention. Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)
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19 pages, 1091 KiB  
Review
Ketogenic Diet and Neuroinflammation: Implications for Neuroimmunometabolism and Therapeutic Approaches to Refractory Epilepsy
by Daniela Guerreiro, Anabela Almeida and Renata Ramalho
Nutrients 2024, 16(23), 3994; https://doi.org/10.3390/nu16233994 - 22 Nov 2024
Cited by 2 | Viewed by 2282
Abstract
Refractory epilepsy, characterized by seizures that do not respond to standard antiseizure medications, remains a significant clinical challenge. The central role of the immune system on the occurrence of epileptic disorders has been long studied, but recent perspectives on immunometabolism and neuroinflammation are [...] Read more.
Refractory epilepsy, characterized by seizures that do not respond to standard antiseizure medications, remains a significant clinical challenge. The central role of the immune system on the occurrence of epileptic disorders has been long studied, but recent perspectives on immunometabolism and neuroinflammation are reshaping scientific knowledge. The ketogenic diet and its variants have been considered an important medical nutrition therapy for refractory epilepsy and may have a potential modulation effect on the immune system, specifically, on the metabolism of immune cells. In this comprehensive review, we gathered current evidence-based practice, ketogenic diet variants and interventional ongoing clinical trials addressing the role of the ketogenic diet in epilepsy. We also discussed in detail the ketogenic diet metabolism and its anticonvulsant mechanisms, and the potential role of this diet on neuroinflammation and neuroimmunometabolism, highlighting Th17/Treg homeostasis as one of the most interesting aspects of ketogenic diet immune modulation in refractory epilepsy, deserving consideration in future clinical trials. Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)
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15 pages, 504 KiB  
Review
Molecular Mechanisms of Biotin in Modulating Inflammatory Diseases
by Mika Sakurai-Yageta and Yoichi Suzuki
Nutrients 2024, 16(15), 2444; https://doi.org/10.3390/nu16152444 - 27 Jul 2024
Cited by 5 | Viewed by 3699
Abstract
Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin and serves as an essential co-enzyme for five specific carboxylases. Holocarboxylase synthase (HCS) activates biotin and facilitates its covalent attachment to these enzymes, while biotinidase releases free biotin in [...] Read more.
Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin and serves as an essential co-enzyme for five specific carboxylases. Holocarboxylase synthase (HCS) activates biotin and facilitates its covalent attachment to these enzymes, while biotinidase releases free biotin in the biotin cycle. The transport of biotin, primarily from the intestine, is mediated by the sodium-dependent multi-vitamin transporter (SMVT). Severe biotin deficiency leads to multiple carboxylase deficiency. Moreover, biotin is crucial to glucose and lipid utilization in cellular energy production because it modulates the expression of metabolic enzymes via various signaling pathways and transcription factors. Biotin also modulates the production of proinflammatory cytokines in the immune system through similar molecular mechanisms. These regulatory roles in metabolic and immune homeostasis connect biotin to conditions such as diabetes, dermatologic manifestations, and multiple sclerosis. Furthermore, deficiencies in biotin and SMVT are implicated in inflammatory bowel disease, affecting intestinal inflammation, permeability, and flora. Notably, HCS and probably biotin directly influence gene expression through histone modification. In this review, we summarize the current knowledge on the molecular aspects of biotin and associated molecules in diseases related to both acute inflammatory responses and chronic inflammation, and discuss the potential therapeutic applications of biotin. Full article
(This article belongs to the Special Issue Impacts of Micronutrients on Immune System and Inflammatory Diseases)
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