Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life

Abstract 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 affect...

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Main Authors: Yu Shimizu, Yuki Yokoi, Shuya Ohira, Hirohisa Izumi, Satomi Kawakami, Miu Ihara, Fuka Tabata, Yasuhiro Takeda, Takashi Kimura, Koshi Nakamura, Akiko Tamakoshi, Tokiyoshi Ayabe, Kiminori Nakamura
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00977-6
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Summary:Abstract 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.
ISSN:2730-664X