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.

Background

Diet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated.

Objective

We evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA).

Methods

We enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6 mo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6 mo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18 mo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA).

Results

Primary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFA + MMN). Mean ± SD α diversity was higher in the LNS group at 18 mo for Shannon index [3.01 ± 0.57 (LNS) compared with 2.91 ± 0.60 (IFA + MMN), P = 0.032] and Pielou's evenness index [0.61 ± 0.08 (LNS) compared with 0.60 ± 0.09 (IFA + MMN), P = 0.043]; no significant differences were observed at 1, 6, 12, or 30 mo. MAZ and β diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFA + MMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%.

Conclusions

Prenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18 mo, after 12 mo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693.

We tested the hypotheses that a more mature or diverse gut microbiota will be positively associated with infant growth and inversely associated with inflammation. We characterized gut microbiota from the stool samples of Malawian infants at 6 mo (n = 527), 12 mo (n = 632) and 18 mo (n = 629) of age. Microbiota diversity and maturity measurements were based on Shannon diversity index and microbiota for age Z-score (MAZ), respectively. Growth was calculated as change in Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HCZ) from 6 to 12 mo and 12 to 18 mo. Biomarkers of inflammation (alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) were measured at 6 and 18 mo. Multivariable models were used to assess the association of each independent variable with each outcome. Microbiota diversity and maturity were related to growth in weight from 6 to 12 mo, but not to growth in length or head circumference or to growth from 12 to 18 mo. Microbiota diversity and maturity may also be linked to inflammation, but findings were inconsistent.