Metallomic Signatures
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
A metallomic signature is the condition-specific profile of trace metals and metal-binding molecules that reflects disrupted metal homeostasis.
Research feed -
Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
FAQs 
Research Feed Overview
Metallomic signatures refer to the condition-specific profile of trace metals and metal-binding molecules that reflect disruptions in metal homeostasis. This signature captures both host and microbial interactions with metals such as iron, zinc, copper, nickel, lead, and cadmium, and is commonly assessed through tissue, blood, or microbiome samples. Metallomic data integrates with other omics layers—such as genomic, metabolomic, proteomic, and microbiome signatures—to illuminate upstream drivers of disease. This is particularly valuable in conditions influenced by environmental exposures, systemic inflammation, or chronic immune activation.
Metallomic Signatures in Pathogenesis and Etiology
A wide array of diseases have been linked to perturbations in metal homeostasis. By comparing the metallomic signatures of healthy versus diseased subjects (or tissues), such the metallomic signatures of neurodegenerative diseases, scientists are uncovering how dysregulated metal levels contribute to disease development and progression.
Relevance to Microbiome Research
Metallomic signatures are deeply connected to microbial metallomics, the study of how microbes acquire, regulate, and utilize metals for metabolic processes and survival. Many pathogenic or dysbiosis-associated taxa rely on metal co-factors like nickel, iron, and zinc to activate virulence factors, resist oxidative stress, or establish biofilms. In metal-enriched environments, these microbes gain a competitive advantage, outcompeting commensals that lack similar metal-handling systems. As a result, metallomic signatures often mirror microbiome signatures, especially in conditions where trace metal excess selects for the expansion of metal-tolerant or metal-dependent microbial taxa.
Clinical Utility
Metallomic signatures provide critical clinical insights by revealing trace metal imbalances that contribute to microbial selection, immune dysregulation, and chronic inflammation. These imbalances can alter the composition and behavior of microbial communities, allowing metal-tolerant pathogens to outcompete metal-sensitive commensals and gain functional advantages. Many of these enriched taxa exploit metals as co-factors for virulence enzymes—such as urease, a nickel-dependent enzyme that facilitates epithelial invasion, immune evasion, and pH modification. Elevated metal levels can therefore establish a biochemical niche that supports both the survival and pathogenicity of harmful species. By identifying these dynamics, metallomic signatures offer a mechanistic framework for understanding the interactions between environmental metal exposure, microbial behavior, and host response. Therapeutic strategies that target metal-induced microbial shifts—such as dietary metal modulation, chelation therapies, or suppression of metal-reliant taxa—not only restore microbial balance but also validate the corresponding microbiome signature. This dual alignment supports precision-guided interventions that are informed by both ecological and biochemical disease mechanisms.
Biomarker Potential
Metallomic signatures are emerging as sensitive, non-invasive biomarkers for disease diagnosis, monitoring, and stratification. These profiles include not only absolute metal concentrations but also natural isotope ratios (e.g., δ66/64Zn), metal–metal interactions, and element-to-element ratios that reflect systemic dyshomeostasis. In diseases such as cancer, COPD, and chronic inflammatory disorders, metallomic patterns involving both toxic and essential metals have demonstrated strong discriminatory power—often exceeding that of conventional biomarkers. Because metal perturbations can occur early in disease progression and remain stable over time, metallomic signatures offer considerable promise for early detection and risk prediction. When applied within microbiome-targeted frameworks, they further aid in identifying pathogenic taxa that depend on specific metals for virulence, thereby reinforcing the validity of both the microbial and metallomic dimensions of disease. Taken together, metallomic signatures provide a rich, actionable layer of insight for both translational research and clinical decision-making.
FAQs
Research Feed
Urine metallomics signature as an indicator of pancreatic cancer†
May 20, 2020
/
Metals •
Metals
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Proin ut laoreet tortor. Donec euismod fermentum pharetra. Nullam at tristique enim. In sit amet molestie
This study identifies a distinct urinary metallomic signature in pancreatic cancer patients, marked by altered calcium, magnesium, copper, and zinc levels, along with lighter zinc isotopic composition. These findings suggest that non-invasive urine tests could enable early PDAC detection by leveraging trace metal imbalances and stable isotope shifts.
What was studied?
This study explored the utility of urinary metallomic profiling—specifically concentrations and isotopic composition of essential metals—as a non-invasive diagnostic tool for pancreatic ductal adenocarcinoma (PDAC). The researchers examined urine samples from PDAC patients and healthy controls to identify specific metal dyshomeostasis and isotopic shifts that could serve as biomarkers for PDAC detection.
Who was studied?
Urine samples from 21 patients diagnosed with PDAC and 46 healthy control subjects were analyzed. All samples were collected under ethical approval through the Barts Pancreas Tissue Bank.
Most important findings:
A distinct urinary metallomic signature was identified in pancreatic ductal adenocarcinoma (PDAC) patients, characterized by decreased calcium and magnesium and increased zinc and copper levels. The multivariate model integrating these four elements exhibited outstanding diagnostic accuracy, achieving an area under the curve (AUC) of 0.995 with 99.5% sensitivity. Moreover, stable zinc isotope analysis revealed a shift toward isotopically lighter zinc in PDAC patients (median δ⁶⁶Zn = −0.15‰) compared to healthy controls (median δ⁶⁶Zn = +0.02‰), likely due to oxidative stress-induced oxidation of cysteine-rich metallothioneins, which preferentially bind lighter isotopes. From a microbiome-metallomic perspective, such trace metal imbalances—particularly involving zinc and copper—may influence microbial community structure by selectively enriching pathogenic taxa and diminishing beneficial ones. Although the microbiome was not directly assessed in this study, the metallomic disturbances observed may serve as indirect indicators of host-microbe dysregulation, especially relevant in gastrointestinal malignancies such as PDAC.
| Element | Change in PDAC vs. Control |
|---|---|
| Calcium (Ca) | Decreased (***p <0.0001) |
| Magnesium (Mg) | Decreased (**p = 0.0002) |
| Zinc (Zn) | Increased (*p = 0.015) |
| Copper (Cu) | Increased (*p = 0.02) |
Greatest implications of the study:
This work provides strong preliminary evidence that urinary metallomic profiles—specifically Ca, Mg, Cu, Zn concentrations and zinc isotopic signatures—can serve as non-invasive biomarkers for PDAC detection. It is the first study to report isotopic zinc alterations in urine associated with PDAC and proposes a compelling mechanistic link to oxidative stress and metalloprotein dysregulation. If validated in larger cohorts, this approach could represent a breakthrough in early detection of pancreatic cancer, a malignancy notorious for its asymptomatic progression and poor prognosis. The authors propose that isotopic measurements, which offer significantly greater resolution than standard clinical assays, could even function as prognostic tools if longitudinally correlated with disease progression.
Microbial Metallomics
Microbial Metallomics is the study of how microorganisms interact with metal ions in biological systems, particularly within the human microbiome.