Preliminary evidence for an influence of exposure to polycyclic aromatic hydrocarbons on the composition of the gut microbiota and neurodevelopment in three-year-old healthy children

Abstract

Background During the second and third year after birth the gut microbiota (GM) is subjected to important development. The polycyclic aromatic hydrocarbon (PAH) exposure could influence the GM in animal and early postnatal exposure is associated with neurodevelopment disorder in children. This study was designed to explore the possible influence of the polycyclic aromatic hydrocarbons (PAHs) on the composition of the gut microbiota (GM) and neurodevelopment in a sample of 38 healthy children at the age of 3 years. Methods A brief development (Gesell Development Inventory, GDI) and behavior test (Child Behavior Checklist, CBCL) were completed on 3-yr-olds and stool samples were collected for 16S rRNA V4-V5 sequencing. The PAH-DNA adduct in the umbilical cord blood and the urinary hydroxyl PAHs (OH-PAHs) at the age of 12 months were measured as pre- and postnatal PAH exposure, respectively. Results The most abundant two phyla were Bacteroidetes (68.6%) and Firmicutes (24.2%). The phyla Firmicutes, Actinobacteria, Proteobacteria, Tenericutes, and Lentisphaerae were positively correlated with most domain behaviors of the GDI, whereas the Bacteroidetes, Cyanobacteria, and Fusobacteria were negatively correlated. Correspondingly, the phyla Bacteroidetes, Actinobacteria, and Fusobacteria showed positive correlations with most CBCL core and broadband syndromes, whereas the Firmicutes, Verrucomicrobia, Synergistetes, Proteobacteria and Tenericules were negatively correlated. The OH-PAH levels were not significantly associated with the Firmicutes phylum whereas the Bacteroidetes, Bacteroidia, and Bacteroidales all showed significant negative association with the OH-PAH levels. Conclusion The current findings suggest that composition of the GM is associated with neurodevelopment of the child. PAHs seem to change the relative abundance of some taxa (some deleted and some recruited) to counteract the negative effects of the PAHs.

Identifying the critical time window for the association of the early-life gut microbiome and metabolome with childhood neurodevelopment

“…However, although validation and mechanistic studies are needed to confirm our findings, we report for the first time a potential two-sided role of Fusobacteria and Fusobacteriota in neurodevelopment with divergent associations with ASQ-Y1 when measured in pregnant mothers compared to during infancy. As for the rest of the shared differential classes between the maternal and infant gut microbiota with respect to the five domains in ASQ-Y1, many of them, including Desulfovibrionia, Gammaproteobacteria, Negativicutes, Bacteriodia, Verrucomicrobiae, Clostridia, Bacilli, Actinobacteria, and Coribacteria, have been related to neurodevelopment in previous studies [35][36][37][38][39][40][41] , which supports the accuracy of our overall findings.…”

Microbiome-gut-brain axis in brain development, cognition and behavior during infancy and early childhood

“…Ruminococcus, Hungatella) to be positively and members of Bacteroidetes phylum (e.g. Porphyromonas, Butyricimonas) to be negatively associated with different subscales, particularly the motor scale, in the Gesell Developmental Inventory (Zhang et al, 2021). These results thus partly parallel those reported by Acuña et al (2021) and suggest that members of the Firmicutes phylum may be positively associated with motor development, however, the specific genera-and species-level associations vary.…”

“…The studies used different measures to assess neurocognitive development, including direct observation with the Mullen Scales of Early Learning (MSEL), Gesell Development Inventory (GDI), and the Bayley Scales of Infant Development (BSID); and parent/caregiver report using the Ages and Stages Questionnaire (ASQ). Two of the studies investigated the potential longitudinal effects of the gut microbiota composition in the first six months after birth on neurodevelopmental outcomes at age 2 to 3 years (Rozé et al, 2020;Sordillo et al, 2019), three studies investigated cross-sectional associations between gut microbiota and neurodevelopment in 18-month-old (Acuña et al, 2021) or 3-year-old children (Rothenberg et al, 2021;Zhang et al, 2021), and two studies used a combination of longitudinal and cross-sectional approaches where either cognitive outcomes (Carlson et al, 2018) or gut microbiota (Kort et al, 2021) were assessed at multiple timepoints. Six of these studies included children born within a normal range of gestation and one studied preterm infants (Rozé et al, 2020).…”

“…Thirteen studies have investigated associations between gut microbiome and socio-emotional development, including temperament, behavioral dysregulation, social behavior, and stress (Table 4). Eleven of these studies have assessed the microbiota composition using 16S rRNA sequencing (Aatsinki et al, 2019(Aatsinki et al, , 2020Carlson et al, 2021;Christian et al, 2015;Fox et al, 2021;Loughman, Ponsonby, et al, 2020;Loughman, Quinn, et al, 2020;Sobko et al, 2020;Sun et al, 2020;Wang et al, 2020;Zhang et al, 2021), one study used whole metagenome sequencing (Kelsey et al, 2021), and one study used both approaches (Laue et al, 2020). The majority of these studies used questionnaires to characterize behavioral development (Infant and Early Childhood Behavior Questionnaire, Child Behavior Checklist (CBCL), Social Responsiveness Scale, Perceived Stress Scale for Children); and three have used direct observational behavioral measures (NICU Network Neurobehavioral Scale, emotional attention paradigm using eye-tracking, and laboratory fear paradigms (Mask Task and Strange Situation)).…”

“…The CBCL is a parent reported questionnaire assessing a broad range of emotional and behavioral problems, and has been used in three studies investigating the relationships between gut microbiome and child development (Loughman, Ponsonby, et al, 2020;Loughman, Quinn, et al, 2020;Zhang et al, 2021).…”