Early-life herbicides exposure with gut microbiota and neurobehavioral development of hospitalized infants in China.

Four specific herbicides were inversely associated with NBNA scores in neonates, primarily affecting behavior and passive tone domains.

• Trifluralin, propyzamide, oxadiazon, and fluazifop-butyl were each inversely associated with NBNA scores (all PFDR < 0.05)
• The associations mainly affected the behavior and passive tone subdomains of the NBNA assessment
• The study cohort consisted of 216 hospitalized neonates
• Herbicide concentrations were measured in neonatal peripheral blood plasma

Mixed herbicide exposure was significantly inversely associated with passive tone scores in the quantile-based g-computation multi-pollutant model.

• QGC model yielded β: -0.105 (95% CI: -0.207, -0.003) for the association between mixed herbicides exposure and passive tone
• Weighted quantile sum regression was also used as a complementary multi-pollutant model
• The association was specifically significant for the passive tone subdomain of neurobehavioral assessment

Bioinformatics analysis identified 183 genes as potential targets for neurodevelopmental disorders associated with herbicides exposure.

• Target genes were retrieved using the CTD and GeneCards databases
• Pathway enrichment analysis indicated these 183 genes were primarily involved in translation, ribosome function, and amino acid and derivative metabolism
• Enrichment pathway analysis was performed following gene target identification

Herbicide exposure significantly altered the infant gut microbiome, with significant differences observed at both phylum and genus levels.

• Significant differences were found in the relative abundances of Proteobacteria and Firmicutes at the phylum level (P < 0.05)
• Significant differences were found in the relative abundances of Escherichia_Shigella and Acinetobacter genera (P < 0.05)
• Gut microbiota was characterized through 16S rRNA sequencing
• Functional pathways were predicted using PICRUSt2

The phenylalanine metabolism pathway was related to herbicide exposure, with upregulation of specific gene expressions in the high exposure group.

• Phenylalanine metabolism was identified as a pathway related to herbicide exposure through PICRUSt2 functional pathway prediction
• Specific gene expressions in this pathway were upregulated in the high herbicide exposure group compared to lower exposure groups
• This pathway falls under amino acid metabolism, consistent with the enrichment pathway analysis findings

No significant associations were observed between gut microbial genera and neurobehavioral scores.

• Associations between taxa abundance and NBNA scores were analyzed using MaAsLin2
• Despite herbicides altering both gut microbiota composition and neurobehavioral scores, no significant link was found between the altered microbiota and neurobehavioral outcomes
• This suggests the gut microbiome may not be a direct mediating pathway between herbicide exposure and neurobehavioral outcomes in this cohort