Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi

Hughes, Riley; Young, Rebecca; Ashorn, Per; Maleta, Kenneth; Fan, Yue‐Mei; Chaima, David; Malamba-Banda, Chikondi; Kable, Mary E.; Dewey, Kathryn G.

doi:10.1038/s41598-020-71922-x

“…These data suggest that this programmed microbial maturation is driven strongly by age, and is robust to changes in WASH and complementary feeding, as delivered in this trial, and that potential microbiome-mediated pathways affecting early-life growth occur independently of these specific interventions. Improvements in growth as a result of the IYCF intervention are not driven by the microbiome, as supported by previous reports showing that the gut microbiome does not mediate the effect of lipid-based IYCF nutrient supplements on child growth 44 . More intensive interventions that target WASH, microbial exposures, nutrient intake and microbiota-directed foods during the first 2 years of life may be required to modify this programmed trajectory of gut microbiome succession.…”

Section: Discussionsupporting

confidence: 74%

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

Robertson

¹

,

Edens²,

Carr

³

et al. 2023

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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.

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“…Our results are in contrast to a previous RCT that investigated infant microbiome composition as a modifier of SQ-LNS impact on infant growth In Malawi 48 . However, in the primary analyses of that RCT, there was no effect of SQ-LNS on linear infant growth 94 .…”

Section: Discussioncontrasting

confidence: 99%

“…Gut microbiota composition, therefore, may also be an important modifier of dietary interventions on infant health. Only one study to date investigated the gut microbiota as an effect modifier of SQ-LNS on infant stunting, and reported limited evidence of effect-modification 48 . However, several studies have reported a synergistic effect of microbiome composition and diet on undernutrition phenotypes using animal models 26,27,49,50 .…”

Section: Introductionmentioning

confidence: 99%

Bifidobacterium longummodifies a nutritional intervention for stunting in Zimbabwean infants

Gough,

Edens,

Carr

et al. 2024

Preprint

0

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Child stunting is an indicator of chronic undernutrition and reduced human capital. However, it remains a poorly understood public health problem. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been widely tested to reduce stunting, but have modest effects. The infant intestinal microbiome may contribute to stunting, and is partly shaped by mother and infant histo-blood group antigens (HBGA). We investigated whether mother-infant fucosyltransferase status, which governs HBGA, and the infant gut microbiome modified the impact of SQ-LNS on stunting at age 18 months among Zimbabwean infants in the SHINE Trial (NCT01824940). We found that mother-infant fucosyltransferase discordance andBifidobacterium longumreduced SQ-LNS efficacy. Infant age-related microbiome shifts inB. longumsubspecies dominance frominfantis, a proficient human milk oligosaccharide utilizer, tosuisorlongum, proficient plant-polysaccharide utilizers, were partly influenced by discordance in mother-infant FUT2+/FUT3- phenotype, suggesting that a "younger" microbiome at initiation of SQ-LNS reduces its benefits on stunting.

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“…These data suggest that this programmed microbial maturation is robust to changes in WASH and complementary feeding, as delivered in this trial, and that potential microbiome-mediated pathways affecting early-life growth occur independently of these specific interventions. Improvements in growth as a result of the IYCF intervention are not driven by the microbiome, as supported by previous reports showing that the gut microbiome does not mediate the effect of lipid-based IYCF nutrient supplements on child growth (39). More intensive interventions that target WASH, microbial exposures, nutrient intake and microbiota-directed foods during the first 2 years of life may be required to modify this programmed trajectory of gut microbiome succession.…”

Section: Discussionsupporting

confidence: 69%

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

Robertson

¹

,

Edens²,

Carr

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

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, and microbiome perturbations may contribute to undernutrition. We examined early-life fecal microbiome composition and function in 875 stool samples collected longitudinally in 335 children from 1-18 months of age in rural Zimbabwe, from a cluster-randomized trial of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF). Using whole metagenome shotgun sequencing, we examined the effect of the interventions, in addition to environmental or host factors including maternal HIV infection, on the succession of the early-life gut microbiome, and employed extreme gradient boosting machines (XGBoost) to model microbiome maturation and to predict child growth. WASH and IYCF interventions had little impact on the fecal microbiome, however children who were HIV-exposed but uninfected exhibited over-diversification and over-maturity of the early-life gut microbiome in addition to reduced abundance of Bifidobacteria species. Taxonomic microbiome features were poorly predictive of linear and ponderal growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predicted both attained linear and ponderal growth and growth velocity. We find that the succession of the gut microbiome in a population at risk of stunting is unresponsive to WASH and IYCF interventions, but is strongly associated with maternal HIV infection, which may contribute to deficits in growth. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.One sentence summaryThe gut microbiome of rural Zimbabwean infants undergoes programmed maturation that is unresponsive to sanitation and nutrition interventions but is comprehensively modified by maternal HIV infection and can moderately predict linear growth.

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Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi

Cited by 9 publications

References 79 publications

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

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

Bifidobacterium longummodifies a nutritional intervention for stunting in Zimbabwean infants

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

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