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. 2024 Jan-Dec;16(1):2290661.
doi: 10.1080/19490976.2023.2290661. Epub 2023 Dec 20.

Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk

Germaine J M Yong  1   2 , Cara E Porsche  1 , Alexandra R Sitarik  3 , Kei E Fujimura  1   4 , Kathryn McCauley  1 , Dat T Nguyen  1   5 , Albert M Levin  3 , Kimberley J Woodcroft  3 , Dennis R Ownby  6 , Andrew G Rundle  7 , Christine C Johnson  3 , Andrea Cassidy-Bushrow  3 , Susan V Lynch  1
Affiliations

Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk

Germaine J M Yong et al. Gut Microbes. 2024 Jan-Dec.

Abstract

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.

Keywords: Early life; childhood obesity; gut barrier dysfunction; gut microbiome; nutrition.

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Conflict of interest statement

S.V.L. is a cofounder, consultant and serves on the board of directors of Siolta Therapeutics Inc.

Figures

Figure 1.
Figure 1.
Compositionally distinct gut microbiota classes (GMCs) in feces of 1-month-old infants exhibit differential microbiota maturity and relate to the relative risk (RR) of overweight/obesity (OW/OB) at age 2 years.
Figure 2.
Figure 2.
High-risk GMC3 and lower-risk GMC1 exhibit distinct metabolic productivity and functional capacities.
Figure 3.
Figure 3.
Cell-free fecal products from GMC3 infant microbiomes who developed OW/OB phenotypes in childhood reprogram Caco-2 enterocyte transcription.
See this image and copyright information in PMC

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