Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk
Recommended Citation
Yong GJM, Porsche CE, Sitarik AR, Fujimura KE, McCauley K, Nguyen DT, Levin AM, Woodcroft KJ, Ownby DR, Rundle AG, Johnson CC, Cassidy-Bushrow A, and Lynch SV. Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk. Gut Microbes 2024; 16(1):2290661.
Document Type
Article
Publication Date
1-1-2024
Publication Title
Gut Microbes
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.
Medical Subject Headings
Infant; Humans; Child; Pediatric Obesity; Enterocytes; Gastrointestinal Microbiome; Microbiota; Feces
PubMed ID
38117587
Volume
16
Issue
1
First Page
2290661
Last Page
2290661
