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Updated: Sep 17, 2025

Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids
Published on: November 15, 2019
Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
Yu Shimizu1,2,3, Yuki Yokoi1,4, Shuya Ohira1,5
1Innate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.
Background:
Bifidobacterium colonization of the intestine is believed to have beneficial effects on our health from infancy throughout life. However, how particular members of the genus Bifidobacterium colonize the neonatal intestine and whether early-life bifidobacterial colonization affects establishment of Bifidobacterium-rich microbiota in later life remain unanswered. α-Defensin secreted from small intestinal Paneth cells elicits selective bactericidal activities that efficiently kill pathogens while hardly affecting commensals including Bifidobacterium in vitro, thus contributing to intestinal microbiota regulation.
Methods:
One hundred forty-eight fecal samples were serially obtained from 33 children from postnatal 3-5 days to 3 years old, conducting a longitudinal cohort study of mothers and children living in Iwamizawa city, Hokkaido, Japan (SMILE Iwamizawa study). Microbiota composition and secretory level of α-defensin, human defensin 5 (HD5), were assessed to investigate the relationship between HD5 and Bifidobacterium colonization.
Results:
We show that HD5 is associated with colonization of Bifidobacterium in early life from pre-weaning to weaning periods. Furthermore, high relative abundance of Bifidobacterium in the weaning period, which positively correlates with HD5 secretion, is associated with the establishment of Bifidobacterium-rich microbiota at 3 years old, when the intestinal microbiota matures.
Conclusions:
This study suggests the importance of the weaning period in establishing long-lasting homeostasis interwoven with the host innate immunity and Bifidobacterium in the intestinal microbiota.
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