Gut microbiota maturation during early human life induces enterocyte proliferation via microbial metabolites

• Published in: BMC microbiology 2020-07, Vol.20 (1), p.205-205, Article 205
• Main Authors: Dougherty, Michael W, Kudin, Oleksandr, Mühlbauer, Marcus, Neu, Josef, Gharaibeh, Raad Z, Jobin, Christian
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Animals; Animals, Newborn; Babies; Bacilli; Bacteria; Bacteria - chemistry; Bacteria - classification; Bacteria - genetics; Bacteria - isolation & purification; Bile; Bile acid; Bile acids; Biomarkers - metabolism; Biosynthesis; Cell growth; Cell Proliferation; Cell viability; Digestive system; Discriminant analysis; DNA, Bacterial - genetics; DNA, Ribosomal - genetics; E coli; Enterocytes - cytology; Enterocytes - microbiology; Epithelial cells; Epithelium; Feces; Feces - microbiology; Fermentation; Gastrointestinal Microbiome; Gastrointestinal tract; Gene Expression Regulation; Homeostasis; Humans; Infant, Newborn; Infants; Intestinal microflora; Intestine; Maturation; Metabolic pathways; Metabolism; Metabolites; Metabolomics - methods; Mice; Microbial activity; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Network; Organ Culture Techniques; Organoids; Organoids - chemistry; Organoids - cytology; Organoids - microbiology; Phylogeny; Premature Birth - microbiology; Principal components analysis; RNA, Ribosomal, 16S - genetics; rRNA 16S; Sox9 protein; Stem cells; Term Birth; Villus; Vitamins
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-020-01892-7

The intestinal tract undergoes a period of cellular maturation during early life, primarily characterized by the organization of epithelial cells into specialized crypt and villus structures. These processes are in part mediated by the acquisition of microbes. Infants delivered at term typically harbor a stable, low diversity microbiota characterized by an overrepresentation of various Bacilli spp., while pre-term infants are colonized by an assortment of bacteria during the first several weeks after delivery. However, the functional effects of these changes on intestinal epithelium homeostasis and maturation remain unclear. To study these effects, human neonate feces were obtained from term and pre-term infants. Fecal 16S rDNA sequencing and global untargeted LC-MS were performed to characterize microbial composition and metabolites from each population. Murine enteral organoids (enteroids) were cultured with 0.22 μm filtered stool supernatant pooled from term or pre-term infants. Term and pre-term microbial communities differed significantly from each other by principle components analysis (PCoA, PERMANOVA p