Environmental exposures and child and maternal gut microbiota in rural Malawi.

BACKGROUND: Gut microbiota composition is associated with child health, but the effect of the environment on microbiota composition is not well understood. Few studies have been conducted in low-income settings where childhood malnutrition is common and possibly related to microbiota composition. OBJECTIVES: To investigate whether gut microbiota composition in young children and their mothers is associated with different environmental exposures in rural Malawi. We hypothesized that more adverse environmental exposures would be associated with lower levels of microbiota maturity and diversity. METHODS: Faecal samples from up to 631 children and mothers participating in a nutrition intervention trial were collected at 1, 6, 12, 18, and 30 months (children) and at 1 month (mothers) after birth and analysed for microbiota composition with 16S rRNA sequencing. Bacterial OTU and genus abundances, measures of microbiota maturity and diversity, and UniFrac distances were compared between participants with different environmental exposures. The exposure variables included socio-economic status, water source, sanitary facility, domestic animals, maternal characteristics, season, antibiotic use, and delivery mode. RESULTS: Measures of microbiota maturity and diversity in children were inversely associated with maternal education at 6, 18, and 30 months and did not otherwise differ consistently between participants with different environmental exposures. Phylogenetic distance was related to season of stool sample collection at all time points. At the level of individual OTUs and genera, season of stool sample collection, type of water source, and maternal education showed most associations with child gut microbiota, while HIV status was the most important predictor of relative OTU and genus abundances in mothers. CONCLUSION: The results do not support the hypothesis that adverse environmental exposures are broadly associated with lower microbiota maturity and diversity but suggest that environmental exposures influence the abundance of several bacterial OTUs and genera and that low maternal education is associated with higher microbiota maturity and diversity.

Co-causation of reduced newborn size by maternal undernutrition, infections, and inflammation.

More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest. We tested a hypothesis that in low-income settings, newborn size is influenced jointly by multiple maternal exposures and characterized pathways associating these exposures with newborn size. This was a prospective cohort study of pregnant women and their offspring nested in an intervention trial in rural Malawi. We collected information on maternal and placental characteristics and used regression analyses, structural equation modelling, and random forest models to build pathway maps for direct and indirect associations between these characteristics and newborn weight-for-age Z-score and length-for-age Z-score. We used multiple imputation to infer values for any missing data. Among 1,179 pregnant women and their babies, newborn weight-for-age Z-score was directly predicted by maternal primiparity, body mass index, and plasma alpha-1-acid glycoprotein concentration before 20 weeks of gestation, gestational weight gain, duration of pregnancy, placental weight, and newborn length-for-age Z-score (p < .05). The latter 5 variables were interconnected and were predicted by several more distal determinants. In low-income conditions like rural Malawi, maternal infections, inflammation, nutrition, and certain constitutional factors jointly influence newborn size. Because of this complex network, comprehensive interventions that concurrently address multiple adverse exposures are more likely to increase mean newborn size than focused interventions targeting only maternal nutrition or specific infections.