Overview of Gut Microbiome
The gut microbiome referred to as the “second brain”, plays an important role in the host health, by regulating gut endocrine function and neural signaling, and facilitating food digestion and metabolism of xenobiotics.
It is critical for the gut microbial colonization and establishment of homeostasis during the early stage of life. This process will shape the characteristics of the gut microbiome throughout childhood, adulthood, and old age, exerting lifelong impacts on the host health. Evidences indicated the structure and function of the gut microbiome in early life linked to the development of many complex diseases, including neurobehavioural disorders, immune disorders, obesity, and diabetes.
How did the gut microbiome colonize and develop?
The fetus acquires its first microbes from the maternal microbiome, while subsequent vaginal delivery, breastfeeding, skin contact, and environmental exposure introduce new colonizing microbes to the neonatal gut. The gut microbiome diversity then increases rapidly with the introduction of solid foods, reaching a homeostatic equilibrium around three years of age. However, the composition and diversity of the gut microbiome are highly variable, particularly in the early stages of life. Microbial colonization and development are sensitive to internal and external stimuli, including host genes, delivery mode, feeding pattern, antibiotic use, environmental factors, and microbial interactions. This raises the possibility that exposure to environmental pollutants leads to gut dysbiosis.
Current research on the impacts of environmental pollutant exposure on infant gut microbiome remains limited, with the dynamic changes and long-term health effects still poorly understood. Hence, a longitudinal cohort was built in this study: (1) to assess prenatal trace elements exposure levels based on maternal hairs; (2) to elucidate the developmental trajectories of the gut microbiome, metabolome, and resistome during the first year of life; and (3) to investigate the long-term effects of trace elements exposure in early life on the infant gut microbiome, metabolome, and resistome. These findings provide novel insights into the complexity and vulnerability of gut microbiome development in early life.
How was the study conducted?
(1) Recruit: 146 participants were recruited between November 2021 and March 2023, and provided hair samples, demographic information, and clinical records in the postnatal six-week outpatient service.
(2) Postpartum visits: during the regularly scheduled postpartum visits at about 3, 6, and 12 months, mothers were asked to collect paired mother-infant stool samples at home (an infant stool sample in the provided diaper).
(3) Analysis: maternal hair samples were analyzed for trace elements concentrations, while paired maternal-infant stool samples were subjected to 16S rRNA amplicon sequencing, metagenomics, and non-target metabolomics.
Results
During the first year of life, infants and their paired mothers have distinct gut microbiome, and their bacterial community structures gradually approach each other as the infant grows older. Delivery mode and feeding pattern were identified as the primary determinants of the infant gut microbiome at 3 and 6 months of age. Shannon diversity of the infant gut microbiome in the high copper exposure group (> 11.6 μg/g) was significantly reduced compared to that of the medium and low exposure groups. Following two postpartum visits, Shannon diversity of the high exposure group showed an apparent and continuing upward trend, especially from 6 to 12 months of age. The relative abundance of Bifidobacterium and Erysipelatoclostridium increased under high exposure to aluminum (> 8.77 μg/g) and manganese (> 0.39 μg/g). However, due to the high variability of the gut microbiome during infancy, prenatal exposure to trace elements had varying effects on specific bacterial taxa at different postpartum visits.
Concurrently, the infant gut metabolome exhibited increased complexity and partial overlap with maternal metabolic profiles. Notably, the dominant genera (e.g., Blautia) were implicated in regulating 49 critical metabolites at 12 months of age, reflecting the coordinated gut microbiome and metabolic programming. Essential and toxic elements (including iron, selenium, and mercury) were also found to participate in regulating infant gut metabolites, such as gluconic acid, citramalic acid, palmitic acid, and 4-trimethylammoniobutanoic acid, which are either important substrates for the production of SCFAs or modulate intestinal immune responses and disease.
Furthermore, we characterized antibiotic resistance gene (ARG) profiles in the gut microbiome of 33 infants and 32 mothers. A total of 263 ARGs were detected and conferred resistance to 33 drug classes. During the first to the third postpartum visit, 150-160 ARGs were overlapping between infants and mothers, and the relative abundance of infant ARG profiles tended to be similar to that of their mothers. Our study found prenatal exposure to trace elements affected the incidence of ARGs, where copper, arsenic, and zinc were positively correlated with multiple ARGs of 6-month-old infants. Emerging evidence positions metals as critical environmental drivers of ARGs dissemination, and this study paves the way in describing the association between trace element exposure and the abundance of ARGs in the gut of the human population.