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Review
. 2022 May 11;30(5):617-626.
doi: 10.1016/j.chom.2022.04.002.

Gut microbiome development and childhood undernutrition

Affiliations
Review

Gut microbiome development and childhood undernutrition

Michael J Barratt et al. Cell Host Microbe. .

Abstract

Forty-five percent of deaths among children under 5 years of age are associated with undernutrition. Globally, almost 200 million children exhibit the two major forms of undernutrition-wasting (low weight-for-height) or stunting (low height-for-age), with many affected by both. Undernutrition is not due to food insecurity alone. Growing evidence indicates that perturbed postnatal gut microbiome development contributes to its pathogenesis. This perspective focuses on defining and repairing these defects in gut microbiome development. We describe an approach that involves the analysis of well-phenotyped human cohorts, followed by preclinical studies using gnotobiotic animals colonized with microbiota from these cohorts. Additionally, these models can be used to identify therapeutic targets and candidates that can then be tested clinically. Furthermore, introducing pretreatment microbiota from trial participants into gnotobiotic animals and re-enacting trial conditions allow mechanisms to be dissected. We highlight these recent advances as well as gaps in existing knowledge that present opportunities for future research.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests. The authors have patent applications related to the use of MDCF-2 and B. infantis Bg_2D9 for the treatment of malnutrition.

Figures

Figure 1.
Figure 1.. A translational medicine pipeline for delineating the contributions of the human gut microbiome to undernutrition, identifying therapeutic targets, and developing therapeutic candidates.
(A) Schematic of the pipeline. (B) Hypotheses and considerations related to the pipeline.
Figure 2.
Figure 2.. Effects of MDCF-2 intervention on ponderal growth-associated fecal bacterial taxa and the plasms proteins in Bangladeshi children with MAM
(A) Coefficients of linear mixed effects model (± SEM) showing bacterial amplicon sequence variants (ASV) significantly correlated with ponderal growth (weight-for-length Z-score; WLZ). (B) Differential effects of MDCF-2 and RUSF on WLZ-associated proteins. Proteins are ordered by the log2(fold-change) of the treatment effect of MDCF-2 over RUSF after three months of supplementation. Gene set enrichment analysis (GSEA) was used to calculate the enrichment of proteins whose abundances were increased more by MDCF-2 compared to RUSF for the set of proteins that were positively correlated with WLZ. The top 30 proteins are shown. Adapted from Chen et al., 2021.
Figure 3.
Figure 3.. The top 10 positive correlations between the abundances of environmental enteric dysfunction (EED)-associated small intestinal taxa and levels of duodenal proteins in biopsies from a cohort of stunted Bangladeshi children (BEED study) with histopathological evidence of EED.
A larger size and darker color circle represent a stronger correlation. Adapted from Chen et al., 2020.

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