Maternal exposure to metals rewires infants’ gut and resistance genes

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Jun 5 2025

New research reveals how trace metals mothers are exposed to during pregnancy can shape their babies’ gut bacteria, metabolic pathways, and even antibiotic resistance, potentially influencing lifelong health.

Study: Prenatal exposure to trace elements impacts mother-infant gut microbiome, metabolome and resistome during the first year of life. Image Credit: Anusorn Nakdee / Shutterstock

In a recent study published in the journal Nature Communications, a group of researchers investigated how prenatal exposure to trace elements influences the infant gut microbiome, metabolome, and antibiotic resistance gene profiles in the first year of life.

It is important to note that these findings are based on observational associations and do not establish causality. Unmeasured confounding or other environmental exposures could also influence the observed relationships.

Background

At birth, a newborn's gut is a blank slate; yet, within days, it becomes a complex microbial ecosystem. This early colonization is crucial because the gut microbiome influences everything from digestion to immunity. Vaginal birth, breastfeeding, and environmental exposures affect the development of these microbial communities. However, pollutants such as heavy metals, arsenic, mercury, and lead are pervasive and can cross the placenta. These trace elements have been linked to neurodevelopmental harm, but their impact on the infant gut microbiome remains unclear. Current methods to study prenatal exposure are often invasive. Therefore, further research is needed to investigate how non-invasive indicators, such as maternal hair, reflect exposures that affect early-life gut health.

About the study

Researchers recruited 146 mother-infant pairs in China and collected maternal hair samples six weeks postpartum to assess prenatal exposure to 12 trace elements, including arsenic, lead, mercury, selenium, and copper. Infant and maternal stool samples were collected at three time points, approximately 3, 6, and 12 months after delivery, for 16S ribosomal Ribonucleic Acid (RNA) gene sequencing, metagenomic analysis, and metabolomic profiling. In total, 353 stool samples underwent sequencing, with 65 analyzed using metagenomics and 198 analyzed for metabolomics. Hair sample data were available for 119 mothers, 83 of whom were matched with stool samples.

Microbial diversity was assessed using indices like Shannon and Chao1. Statistical methods, including linear regression and stratified analysis, were used to detect associations between trace element concentrations and microbial metrics. Antibiotic resistance gene (ARG) profiles were analyzed in stool samples from 33 infants and 32 mothers using metagenomic approaches. Metabolomic analyses identified over 3,800 metabolites across stool samples, and correlations between microbial taxa and metabolites were explored using Spearman correlation. The development of the infant gut microbiome was tracked over time and compared to maternal profiles. Differential abundances of microbes and metabolites were assessed using linear discriminant analysis, and data were adjusted for multiple comparisons to ensure statistical accuracy.

Study results

The infant gut microbiome undergoes significant evolution during the first year, transitioning from a community dominated by Bifidobacterium and Escherichia-Shigella to one that increasingly resembles the maternal gut. Microbial diversity, initially lower in infants, increased over time. While maternal microbiomes remained relatively stable, infant microbiomes showed dynamic changes, especially between 6 and 12 months of age. At 12 months, the composition of infant microbial communities began to converge more closely with that of their mothers, suggesting a shift.

Delivery mode and feeding patterns played a critical role in shaping early microbial communities. Forceps-assisted delivery was associated with higher diversity indices. Breastfeeding also significantly influenced bacterial composition. These effects, however, diminished by 12 months, indicating that other factors, such as diet, gradually moderate initial environmental influences.

Prenatal exposure to trace elements had measurable effects. Selenium exposure was associated with increased microbial diversity, while copper and mercury were linked to decreased diversity. In male infants, manganese exposure increased microbial richness, while in female infants, mercury reduced diversity. Some associations were observed only in specific contexts, such as increased diversity with arsenic exposure among forceps-delivered infants, or positive associations between iron exposure and microbial diversity among mix-fed infants. Not all trace elements showed statistically significant associations in the general cohort. Stratified analysis further revealed that specific exposures influenced microbial diversity differently depending on delivery mode and feeding pattern.

When comparing groups with low, medium, and high exposure to trace elements, copper stood out. High prenatal copper exposure resulted in significantly lower microbial diversity at 3 months, although this effect diminished over time. Bacterial taxa also shifted in response to exposures. For example, aluminum exposure increased Bifidobacteria and Cutibacteria, but did not alter overall microbial diversity. Manganese and lead exposure altered the levels of Erysipelatoclostridium and Ruminococcus gnavus. Iron exposure was associated with a decrease in Enterococcus abundance.

Metabolomic analysis revealed 56 significantly altered metabolites between 3 and 6 months, and 515 between 6 and 12 months. These included changes in fatty acids, carbohydrates, bile acids, and flavones. Some metabolites, such as lacto-N-fucopentaose III, were associated with specific bacterial taxa, including Streptococcus and Blautia. Prenatal exposure to selenium and cadmium was associated with shifts in metabolite concentrations, suggesting that trace elements impact not only microbial composition but also microbial function.

Trace elements also shaped antibiotic resistance gene profiles. A total of 263 ARGs were identified. Infants showed a higher abundance of tetracycline and fluoroquinolone resistance genes, while mothers had a higher abundance of macrolide and lincosamide resistance genes. Copper and arsenic exposures were associated with elevated ARGs, such as the Aminoglycoside efflux pump D (acrD) and the Multidrug transporter subunit B (mdtB), especially by 6 months of age. Despite some overlap, infant ARG profiles were distinct from those of their mothers, although convergence was observed over time. Some associations between trace elements and ARG profiles were statistically significant only in specific age groups or exposure categories.

Conclusions

To summarize, this study reveals that prenatal exposure to trace elements, including selenium, copper, manganese, and arsenic, significantly alters the gut microbiome, metabolome, and antibiotic resistance gene profiles in infants. These changes are detectable as early as three months and continue to evolve during the first year of life.

The findings underscore the importance of prenatal environmental exposures in shaping early gut development and their potential impact on long-term health outcomes. Non-invasive sampling through maternal hair offers a valuable method for monitoring these exposures.

Given the observational nature of the study, further research is needed to establish causal relationships and to identify the underlying mechanisms. Intervening early to reduce harmful exposures could support healthier microbiome development and potentially reduce future disease risks.