The gut microbiome and early-life growth in a population with high prevalence of stunting.

Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1-18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition

The role of the infant microbiota and childhood stunting in rural Zimbabwe

Childhood stunting or linear growth failure is a major global health issue, affecting 22% of children under 5 years of age worldwide. Stunting impacts people across the life course. Stunting is associated with a greater number of infections, reduced childhood survival, impaired cognitive development, and reduced adulthood productivity, and contributes to an intergenerational cycle of poor growth and development. Decreased linear growth has been associated with community-level changes in the gut microbiome as well as specific changes in individual bacterial and decreased overall microbial diversity. However, the literature addressing the role of the gut microbiome on poor child linear growth is limited. We conducted an analysis of the infant fecal microbiota composition from 1-18 months of life from infants participating in the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) Trial, a large cluster-randomized trial, designed to evaluate the impact of improved household water quality, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on linear growth and anaemia during the first 18 months of infant life in rural Zimbabwe. Using whole metagenomic sequencing, we were able to describe the infant fecal microbiota composition of SHINE Trial infants and examine relationships between the microbiota composition and HIV exposure status, SHINE trial interventions, and stunting status. As expected, age was the major driver of microbiota composition and diversity. No major differences in the infant fecal microbiota by HIV exposure status, SHINE trial interventions, or stunting status were observed. These results highlight the complex nature of linear growth and demonstrate that infant fecal microbiota composition plays a smaller direct role on growth in SHINE infants. Our study also confirms that the SHINE WASH intervention did not influence infant growth through alterations to the fecal microbiota composition, confirming the primary SHINE results. However, the functional potential of the infant fecal microbiota of SHINE infants will be examined in future analyses; this may uncover relationships separate from microbiota composition and diversity alone.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat