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Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

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posted on 20.09.2017 by Yu Y, Lu L, Sun J, Petrof EO, Claud EC
Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

Funding

This work was supported by the National Institute Health of Child Health and Human Development Grants R01 HD059123 (ECC) and R01 HD083481 (ECC) and the Digestive Disease Research Core Center of the University of Chicago grant (P30DK42086).

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Publisher Statement

This is a non-final version of an article published in final form in Yu, Y. Y., Lu, L., Sun, J., Petrof, E. O. and Claud, E. C. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2016. 311(3): G521-G532. DOI:10.1152/ajpgi.00022.2016.

Publisher

American Physiological Society

issn

0193-1857

Issue date

01/09/2016

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