Effect of diarrhea on early-life gut microbiome composition and subsequent infant growth in Beira, Mozambique: analysis of the PAASIM longitudinal birth cohort.

BACKGROUND

The first year of life is a critical period for gut microbiome maturation; however, the interplay between diarrheal burden, microbial development, and growth in high-burden settings remains poorly understood.

OBJECTIVES

We leveraged longitudinal data from the Pesquisa Sobre o Acesso à Água e a Saúde Infantil em Moçambique (PAASIM) longitudinal birth cohort study in Beira, Mozambique, to test whether diarrhea is associated with gut microbiome characteristics and whether microbiome profiles relate to infant growth.

METHODS

Stool samples collected at 3, 6, 9 (n ∼150 at each time point), and 12 (n = 536) mo underwent 16S rRNA gene sequencing, with microbial diversity and taxonomic composition analyzed alongside monthly caregiver-reported diarrhea and anthropometric measurements.

RESULTS

Alpha diversity increased across infancy, and beta diversity shifted significantly with age, consistent with the ongoing maturation of the microbiome. Cumulative period prevalence of diarrhea from birth to 12 mo was not associated with microbial diversity or community composition at 12 mo. Higher alpha diversity at 3 mo was positively associated with length-for-age z-scores (LAZ) at 12 mo [β coefficient: 1.49; 95% confidence interval (CI): 0.33, 2.67], whereas higher diversity at 6 mo was inversely associated with LAZ at 12 mo (β: -2.85; 95% CI: -4.25, -1.45), showing age-dependent relationships with later linear growth. At 12 mo, we observed small beta-diversity differences between wasted and nonwasted (permutational multivariate analysis of variance, PERMANOVA R2 = 0.05, P = 0.012) and between stunted and nonstunted children (R2 = 0.05, P = 0.014). An exploratory longitudinal analysis revealed a positive association between Finegoldia abundance and wasting at 12 mo (β = 1.66; 95% CI: 0.83, 2.48), which met multiple-testing thresholds [false discovery rate = 0.19].

CONCLUSIONS

These findings suggest that early microbial trajectories, independent of cumulative diarrheal burden, may be linked to growth outcomes, warranting further research to identify potential microbiome-targeted interventions in the first year of life, a pivotal window for promotion of healthy growth in resource-limited settings.