The influence of pre- and postnatal exposure to air pollution and green spaces on infant's gut microbiota: Results from the MAMI birth cohort study.

BACKGROUND: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. OBJECTIVES: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. METHODS: MAMI ("MAternal MIcrobes") birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. RESULTS: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. DISCUSSION: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut microbial composition. Further research is needed to confirm these findings.

The role of Bifidobacterium genus in modulating the neonate microbiota: implications for antibiotic resistance acquisition in early life.

Resistance to antibiotics in newborns is a huge concern as their immune system is still developing, and infections and resistance acquisition in early life have short- and long-term consequences for their health. Bifidobacterium species are important commensals capable of dominating the infant gut microbiome and are known to be less prone to possess antimicrobial resistance genes than other taxa that may colonize infants. We aimed to study the association between Bifidobacterium-dominated infant gut microbiota and the antibiotic resistant gene load in neonates, and to ascertain the perinatal factors that may contribute to the antibiotic resistance acquisition. Two hundred infant fecal samples at 7 days and 1 month of age from the MAMI birth cohort were included in the study and for whom maternal-neonatal clinical records were available. Microbiota profiling was carried out by 16S rRNA amplicon sequencing, and targeted antibiotic resistance genes (ARGs) including tetM, tetW, tetO, blaTEM, blaSHV and ermB were quantified by qPCR. Infant microbiota clustered into two distinct groups according to their Bifidobacterium genus abundance: high and low. The main separation of groups or clusters at each time point was performed with an unsupervised non-linear algorithm of k-means partitioning to cluster data by time points based on Bifidobacterium genus relative abundance. Microbiota composition differed significantly between both groups, and specific bifidobacterial species were enriched in each cluster. Lower abundance of Bifidobacterium in the infant gut was associated with a higher load of antibiotic resistance genes. Our results highlight the relevance of Bifidobacterium genus in the early acquisition and establishment of antibiotic resistance in the gut. Further studies are needed to develop strategies to promote a healthy early colonization and fight against the spread of antibiotic resistances.

Role of vertical and horizontal microbial transmission of antimicrobial resistance genes in early life: insights from maternal-infant dyads.

Early life represents a critical window for metabolic, cognitive and immune system development, which is influenced by the maternal microbiome as well as the infant gut microbiome. Antibiotic exposure, mode of delivery and breastfeeding practices modulate the gut microbiome and the reservoir of antibiotic resistance genes (ARGs). Vertical and horizontal microbial gene transfer during early life and the mechanisms behind these transfers are being uncovered. In this review, we aim to provide an overview of the current knowledge on the transfer of antibiotic resistance in the mother-infant dyad through vertical and horizontal transmission and to highlight the main gaps and challenges in this area.

Old Folks, Bad Boon: Antimicrobial Resistance in the Infant Gut Microbiome.

The development of the intestinal microbiome in the neonate starts, mainly, at birth, when the infant receives its founding microbial inoculum from the mother. This microbiome contains genes conferring resistance to antibiotics since these are found in some of the microorganisms present in the intestine. Similarly to microbiota composition, the possession of antibiotic resistance genes is affected by different perinatal factors. Moreover, antibiotics are the most used drugs in early life, and the use of antibiotics in pediatrics covers a wide variety of possibilities and treatment options. The disruption in the early microbiota caused by antibiotics may be of great relevance, not just because it may limit colonization by beneficial microorganisms and increase that of potential pathogens, but also because it may increase the levels of antibiotic resistance genes. The increase in antibiotic-resistant microorganisms is one of the major public health threats that humanity has to face and, therefore, understanding the factors that determine the development of the resistome in early life is of relevance. Recent advancements in sequencing technologies have enabled the study of the microbiota and the resistome at unprecedent levels. These aspects are discussed in this review as well as some potential interventions aimed at reducing the possession of resistance genes.

Maternal-infant antibiotic resistance genes transference: what do we know?

Resistance to antibiotics is becoming a worldwide threat as infections caused by multidrug-resistant pathogenic microorganisms can overcome antibiotic treatments and spread quickly in the population. In the context of early life, newborns are at increased risk as their immune system is still under development, so infections and acquisition of resistance during childhood have short- and long-term consequences for the health. The moment of birth is the first exposure of infants to possible antibiotic-resistant microorganisms that may colonize their gut and other body sites. Different factors including mode of delivery, previous antibiotic exposure of the mother, gestational age and consumption of antibiotics in early-life have been described to modulate the neonate's microbiota, and thus, the resistome. Other factors, such as lactation, also impact the establishment and development of gut microbiota, but little is known about the role of breastmilk in transferring Antibiotic Resistant Genes (ARG). A deeper understanding of vertical transmission of antibiotic resistance from mothers to their offspring is necessary to determine the most effective strategies for reducing antibiotic resistance in the early life. In this review, we aim to present the current perspective on antibiotic resistances in mother-infant dyads, as well as a new insight on the study of the human gut and breastmilk resistome, and current strategies to overcome this public health problem, toward highlighting the gaps of knowledge that still need to be closed.