Metallomics Reviews
Pediatric Gut Microbiome Composition in Health: A Systematic Review
Clinical Overview
This systematic review synthesizes 42 studies (>2000 children, 2–12 years) characterizing the fecal gut microbiome of healthy preadolescents using 16S rRNA sequencing or metagenomics. The pediatric gut is dominated by Firmicutes (51.1%) and Bacteroidetes (36.0%), with Actinobacteria (5.98%) and Proteobacteria (2.93%) as minor phyla. Geographic region and 16S hypervariable region strongly shape observed community structure; age within 2–12 years has limited impact. Short-chain fatty acids (SCFAs) in stool vary widely, but rural, high-fiber cohorts consistently show higher total SCFAs. A Tanzanian cohort of children exposed to heavy metals showed Prevotellaceae-dominated microbiota and no major compositional shift with probiotic yogurt.
What was reviewed and who was studied
The review collates fecal microbiome data from healthy or overweight/obese but otherwise disease-free children aged 2–12 years across Africa, Asia, Europe, North and Central America, including one Tanzanian cohort explicitly exposed to toxic metals and a separate African trial of iron fortification. All studies used molecular methods (16S rRNA amplicon sequencing or whole-genome shotgun) to profile gut community composition; a minority also quantified fecal SCFAs using gas chromatography–mass spectrometry, liquid chromatography, or capillary electrophoresis.
Major findings
| Domain | Summary of findings |
|---|---|
| Taxonomic composition (phylum) | Across 18 studies with phylum-level data, Firmicutes (51.1%) and Bacteroidetes (36.0%) dominate, followed by Actinobacteria (5.98%) and Proteobacteria (2.93%); Verrucomicrobia, Tenericutes, and Fusobacteria are present at low abundance. |
| Taxonomic composition (family/genus) | Fecal communities are enriched in Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, Prevotellaceae, and Bifidobacteriaceae; key genera include Bacteroides (16.0%), Prevotella (8.69%), Faecalibacterium (7.51%), and Bifidobacterium (5.47%). |
| Geography and diet | African and Central American children show lower Firmicutes and higher Bacteroidetes, with high Prevotellaceae (e.g., 46.5% in one African cohort) and higher fecal SCFAs, consistent with high-fiber diets. Urbanized Asian cohorts resemble Western children. |
| Age effects (2–12 years) | Within this age band, relative Firmicutes and Bacteroidetes proportions stabilize; Actinobacteria and Bifidobacterium generally decline with age while Proteobacteria rise, but α- and β-diversity show no consistent age trend. |
| Methodological effects | 16S region strongly affects apparent composition: V6-based studies show higher Firmicutes and Actinobacteria than V4; V1–V3 yields higher Proteobacteria and large “unknown” fractions. Whole-genome data cluster separately in β-diversity analysis. |
| SCFAs and metabolism | Rural, high-fiber cohorts (e.g., Burkina Faso and rural Thailand) have significantly higher fecal total SCFAs, acetate, propionate, and butyrate than Western or urban peers, but absolute concentrations vary widely due to heterogeneous extraction and detection protocols. |
Implications for Microbial Metallomics
The pediatric gut metallome will be embedded in a Firmicutes–Bacteroidetes–Prevotella–Bifidobacterium framework that is strongly shaped by geography, diet, and sequencing methods rather than age alone.
| Concept | Implication |
|---|---|
| Prevotella-rich, high-fiber rural microbiomes | Tanzanian, Burkinabé, and other rural cohorts show Prevotellaceae dominance and high SCFAs, providing a distinct metabolic and likely metal-binding milieu compared with Bacteroides-dominated Western children; metal-exposure studies must stratify by these enterotype-like structures. |
| Heavy metal–exposed Tanzanian children | In the only explicitly metal-exposed cohort, probiotic yogurt did not significantly alter community composition, indicating that bulk 16S profiles may be relatively insensitive to modest microbiome-directed metal interventions and that metal endpoints must be measured directly. |
| Iron fortification trial in African children | Iron fortification was included among pediatric microbiome studies, highlighting dietary metal exposure as a common, clinically relevant perturbation; future metallomics work should pair iron speciation/kinetics with standardized microbiome profiling. |
| Decline in Bifidobacterium with age | The age-related drop in Bifidobacterium and rise in Proteobacteria across childhood suggests that metal uptake, detoxification, and redox cycling may shift with development, even in the absence of disease, altering susceptibility to metal toxicity. |
| SCFA–microbiome coupling | High SCFA output in Prevotella-rich communities reflects vigorous fermentation of fiber; this may co-occur with specific metal chelation and pH profiles in the colon, influencing metal solubility and microbe–host metal exchange. |
| Methodological heterogeneity | Large differences between 16S regions and analytic pipelines mean that apparent taxonomic shifts in metal-exposed cohorts may partly reflect primer and database choices; metallomics studies need harmonized sequencing and SCFA/metal measurement protocols. |
Limitations
The review aggregates heterogeneous studies with varied sampling strategies, DNA extraction methods, sequencing platforms, hypervariable regions, and bioinformatic pipelines, which markedly alter observed community structure. Many datasets provide incomplete taxonomic resolution, with large “unknown” fractions at family and genus levels. Dietary data are sparse and inconsistent, limiting adjustment for key covariates. SCFA measurement approaches differ substantially (extraction, derivatization, detection, internal standards), undermining between-study comparisons of concentrations. Metals are present chiefly as contextual exposures (toxic metals, iron fortification) without systematic reporting of metal species, doses, or metal–microbiome effect sizes.
Future perspectives
Next studies should integrate standardized fecal microbiome workflows (preferably harmonized 16S regions or metagenomics with shared databases) with rigorous dietary assessment and targeted metabolite panels, including SCFAs and clinically relevant metals such as iron and environmental toxicants. Within cohorts already characterized as Prevotella- or Bacteroides-dominated, controlled metal exposures or interventions could dissect how community structure modifies metal handling and toxicity. Parallel measurement of fecal and blood metals, together with microbiome and SCFA data, would enable mechanistic models of microbe–metal–host interactions in children. Incorporating metabolomics or function inference tools can help link compositional shifts to metal-relevant metabolic capacity.
Key takeaways for Researchers and Clinicians
This systematic review describes the fecal microbiome of healthy children aged 2–12 years across multiple continents, showing a relatively stable Firmicutes–Bacteroidetes core with context-dependent enrichment of Prevotella, Bifidobacterium, and Faecalibacterium. Metals appear mainly as background exposures (heavy metals in Tanzanian children and iron fortification in African trials), with no consistent microbiome shift attributed to these metals at the 16S level.
For microbial metallomics, the key message is that geography, diet, and sequencing methodology outweigh age in shaping the pediatric gut community, and that rural, high-fiber, Prevotella-rich microbiomes generate higher SCFAs than Western, Bacteroides-rich counterparts. Clinically, any attempt to use microbiome signatures for metal‐exposure diagnostics or probiotic/metal-binding therapies in children must account for these strong ecological and technical determinants and should measure metals and metabolites directly rather than inferring them from composition alone. A practical translational hook is that “enterotype plus SCFA profile” may prove more informative than taxonomy alone for understanding metal risk and designing gut-targeted interventions in pediatrics.
Citation
Deering KE, Devine A, O’Sullivan TA, Lo J, Boyce MC, Christophersen CT. Characterizing the Composition of the Pediatric Gut Microbiome: A Systematic Review. Nutrients. 2020;12(1):16