Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This review article synthesizes scientific findings on how iron homeostasis shapes and is shaped by interactions between the host and gut microbiome, with direct implications for disease outcomes and therapeutic strategies. The focus keyphrase “iron at the crossroads of host microbiome interactions” is central to this review, as it encapsulates the complex, bidirectional relationships among dietary iron, the host’s regulatory mechanisms, and the microbial community in the gut. The article comprehensively covers mechanisms of iron regulation in the host, microbial iron acquisition strategies, the influence of microbiota-derived metabolites on iron absorption, and the connection between iron dysregulation, dysbiosis, and human diseases such as infection, inflammatory bowel disease (IBD), and cancer. The review further highlights how dietary factors, medications, and environmental exposures modulate iron availability and, consequently, microbiome composition. This multifaceted perspective is essential for programs like Heavy Metal Tested and Certified (HTMC), as it provides a mechanistic understanding vital for risk assessment and regulatory policy development concerning heavy metals, especially iron.
Who was reviewed?
The review draws on a diverse body of research involving both human and animal studies, as well as in vitro and in vivo models. It considers data from clinical trials in infants, children, and adults, alongside mechanistic and genetic mouse models designed to dissect the roles of iron and the microbiota. Key microbial groups discussed include commensal and pathogenic bacteria such as Bifidobacterium, Lactobacillus, Escherichia coli, Salmonella, and Bacteroides, as well as commensal fungi. The studies reviewed encompass healthy individuals, patients with iron deficiency, iron overload, IBD, and cancer, and those receiving iron supplementation or exposed to drugs affecting iron metabolism. This broad scope ensures that the review’s conclusions are relevant across different populations and clinical contexts, supporting the generalizability of its implications for regulatory frameworks like HTMC.
Most important findings
| Finding Area | Key Details and Relevance for Heavy Metal Certification Standards |
|---|---|
| Host Iron Regulation | Humans maintain iron homeostasis via dietary absorption, sequestration by proteins (hepcidin, calprotectin, lactoferrin, lipocalin-2, haemopexin), and tightly regulated transporters (DMT1, ferroportin). Disruption leads to inflammation, altered immunity, and susceptibility to infection. |
| Microbial Iron Acquisition | Pathogens and commensals employ siderophores and specific uptake systems to compete for iron. Siderophore piracy and stealth siderophores allow evasion of host defenses. Commensal bacteria can enhance or limit iron availability, affecting both pathogen resistance and host health. |
| Microbiota Impact on Iron Absorption | Microbial metabolites—phytases, organic acids, SCFAs, and others—increase or decrease iron bioavailability and absorption. Some probiotics enhance iron uptake, while others (like Bifidobacterium) modulate hepcidin and may lower inflammation. |
| Iron Dysregulation and Disease | Both iron deficiency and overload disrupt microbiota composition. Iron supplements can exacerbate dysbiosis and inflammation, especially in IBD or cancer contexts. Drugs and dietary components (phytates, polyphenols, PPIs) also critically alter iron status and microbiome balance. |
| Personalized Interventions | The interplay between baseline microbiome, diet, and iron regulation means that population-wide recommendations may be ineffective or harmful. Precision approaches targeting both iron status and microbiome composition are necessary for optimal outcomes. |
Key implications
These findings underscore the necessity for heavy metal certification programs like HTMC to integrate microbiome and host iron regulation knowledge into standards and risk assessments. Iron bioavailability, microbiota composition, and host factors must be considered together, as interventions (e.g., supplementation, drug use) can unpredictably alter disease risk, microbial ecology, and host health. Regulatory frameworks should promote personalized, evidence-based guidelines that reflect the complexity of iron–microbiome–host interactions. For industry, this means moving beyond single-nutrient models and considering the broader ecological and physiological context of heavy metal exposure and management.
Citation
Choi G, Bessman NJ. Iron at the crossroads of host–microbiome interactions in health and disease. Nat Microbiol. 2025; https://doi.org/10.1038/s41564-025-02001-y
Heavy metals are high-density elements that accumulate in the body and environment, disrupting biological processes. Lead, cadmium, arsenic, mercury, nickel, tin, aluminum, and chromium are of greatest concern due to persistence, bioaccumulation, and health risks, making them central to the HMTC program’s safety standards.
