Metallomic profiles of pregnant women living with obesity in the UK (UPBEAT secondary analysis): a Review

What was reviewed and who was studied

This paper presents an exploratory, secondary analysis of mid-gestation serum “metallo-profiles” in 755 pregnant women with obesity from the UPBEAT randomized trial in the UK. Eighteen elements were quantified in baseline serum collected at 15–18+6 weeks, followed by association testing with maternal characteristics and perinatal outcomes, using ICP-MS with rigorous QC and batch correction. Visual summaries include the study schematic and cohort descriptors, correlation heatmaps and element-element networks, and outcome associations .

Major findings

The concentration landscape was dominated by Na, K, P, and Ca, with Co at the lowest mean levels. Multiple adjusted associations were identified: higher BMI correlated with higher Cu and Ba, while higher parity associated with lower Ca, Fe, and Mg; Se increased with age and with healthier dietary patterns. Element-element correlations were strong for Ca–Na and Ca–Mg, and varied by ethnicity, diet, and geography. Critically for outcomes, higher mid-pregnancy Mn and Sr associated with antepartum haemorrhage after 34 weeks, and higher maternal P associated with neonatal intensive care unit admission. These signals appear in the outcome heatmaps and boxplots and are detailed in logistic regression tables.

Implications for Microbial Metallomics

The metallomic findings from the UPBEAT secondary analysis provide a foundational framework for integrating elemental homeostasis into microbiome research during pregnancy. Patterns of essential metal variation by BMI, parity, diet, and geography underscore the dynamic interface between the host’s systemic metallome and microbial metal utilization pathways. These relationships not only reveal the biochemical constraints shaping microbial ecology within the maternal environment but also suggest actionable hypotheses for translational research that bridges metallomics, microbiomics, and clinical outcomes. The table below summarizes the three major implications for microbial metallomics emerging from this work.

Concept	Implications for Microbial Metallomics
Host metallome as context for host–microbe chemistry in pregnancy	Variations in essential metals such as Fe, Zn, Ca, Mg, and Na across BMI, parity, diet, and geography indicate altered cofactor availability that may influence microbial metabolism, virulence, and redox balance. Strong element covariations (e.g., Ca–Mg, Ca–Na) suggest systemic coordination that could modulate microbial metalloenzymes, transporters, and nutrient immunity within maternal niches.
Outcome-linked metals as hypotheses for microbe–host interactions	The associations between elevated maternal Mn and antepartum haemorrhage and between elevated P and neonatal intensive care admission point to potential microbial mechanisms involving Mn-dependent enzymes (e.g., superoxide dismutase), phosphate-regulated virulence, and siderophore signaling. These findings provide rational starting points for longitudinal microbiome–metallome analyses exploring microbial metal utilization, speciation, and metalloproteomic shifts during gestation.
Translational measurement frameworks	The validated ICP-MS methodology, internal standardization, and ComBat batch correction protocols offer a reproducible foundation for future microbiome-metallome integration. Establishing harmonized pipelines for serum or tissue metal quantification will support translational clinical studies linking microbial metal handling, maternal metal status, and obstetric outcomes.

Limitations

This is an observational, single-timepoint analysis in a high-BMI cohort without a lean or non-pregnant comparator, which limits causal inference and generalizability. Dietary data are partly self-reported. Important covariates such as vitamin D were unavailable. NICU admission reflects multifactorial decisions and may confound associations. Many potentially informative trace elements were below LOQ and excluded.

Future perspectives

Research should integrate paired microbiome data with metallomics to map how metal availability and speciation influence microbial community structure, metalloprotein expression, and metabolite outputs relevant to obstetric outcomes. Longitudinal sampling across trimesters, combined with metal speciation analysis, metal-binding proteomics, and imaging mass spectrometry in placental tissues, would refine mechanistic insight. Interventional studies that safely modulate dietary metal intake or chelation capacity could test whether steering the maternal metallome improves microbiome composition and clinical endpoints. Standardized, multi-center SOPs for pre-analytical handling and batch correction will be key to cross-study synthesis.

Key takeaways for researchers and clinicians

Mid-pregnancy serum metals vary with BMI, parity, diet, and setting; several elements covary in coordinated patterns that are likely biologically meaningful. Higher maternal Mn and P associated with clinically relevant outcomes that merit mechanistic follow-up. The analytical workflow and QC provide a pragmatic foundation for adding metallomics to obstetric microbiome studies and for developing translational biomarkers that consider both metals and microbes.

Citation

Agostinho de Sousa JA, Griffiths A, Dalrymple KV, White SL, von Meyenn F, Poston L, Rigutto-Farebrother J, Flynn AC; on behalf of the UPBEAT Consortium. Metallomic profiles of pregnant women living with obesity in the UK: a secondary analysis of UPBEAT. Metallomics. 2025;17:mfaf031. doi:10.1093/mtomcs/mfaf031