Infant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct.

TitleInfant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct.
Publication TypeJournal Article
Year of Publication2023
AuthorsAdeniyi-Ipadeola, GO, Hankins, JD, Kambal, A, Zeng, X-L, Patil, K, Poplaski, V, Bomidi, C, Nguyen-Phuc, H, Grimm, SL, Coarfa, C, Crawford, SE, Blutt, SE, Speer, AL, Estes, MK, Ramani, S
Date Published2023 May 20

BACKGROUND & AIMS: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent the infant intestinal anatomy and physiological responses.METHODS: We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We validated differences in key pathways through functional studies and determined if these cultures recapitulate known features of the infant intestinal epithelium.RESULTS: RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed as higher expression of enterocytes, goblet cells and enteroendocrine cells in differentiated infant HIEs, and greater numbers of proliferative cells in undifferentiated cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine.CONCLUSIONS: HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex-vivo model to advance studies of infant-specific diseases and drug discovery for this population.

Alternate JournalbioRxiv
PubMed ID37292968
PubMed Central IDPMC10245709
Grant ListU19 AI144297 / AI / NIAID NIH HHS / United States
P42 ES027725 / ES / NIEHS NIH HHS / United States
P30 DK056338 / DK / NIDDK NIH HHS / United States
S10 RR024574 / RR / NCRR NIH HHS / United States
P50 MD015496 / MD / NIMHD NIH HHS / United States
K08 DK131326 / DK / NIDDK NIH HHS / United States
U19 AI116497 / AI / NIAID NIH HHS / United States
S10 OD028480 / OD / NIH HHS / United States
P30 ES030285 / ES / NIEHS NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States