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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author 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
author_facet 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
author_sort Yu Shimizu
collection DOAJ
description 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.
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spelling doaj-art-0a3e64cc2bd54a4089cd2db126389e462025-08-20T04:01:36ZengNature PortfolioCommunications Medicine2730-664X2025-07-015111010.1038/s43856-025-00977-6Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later lifeYu Shimizu0Yuki Yokoi1Shuya Ohira2Hirohisa Izumi3Satomi Kawakami4Miu Ihara5Fuka Tabata6Yasuhiro Takeda7Takashi Kimura8Koshi Nakamura9Akiko Tamakoshi10Tokiyoshi Ayabe11Kiminori Nakamura12Innate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido UniversityInnate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido UniversityInnate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido UniversityR&D Division, Morinaga Milk Industry Co., Ltd.R&D Division, Morinaga Milk Industry Co., Ltd.Graduate School of Life Science, Hokkaido UniversityR&D Division, Morinaga Milk Industry Co., Ltd.R&D Division, Morinaga Milk Industry Co., Ltd.Department of Public Health, Faculty and Graduate School of Medicine, Hokkaido UniversityDepartment of Public Health and Epidemiology, Graduate School of Medicine, University of the RyukyusDepartment of Public Health, Faculty and Graduate School of Medicine, Hokkaido UniversityInnate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido UniversityInnate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido UniversityAbstract 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.https://doi.org/10.1038/s43856-025-00977-6
spellingShingle 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
Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
Communications Medicine
title Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
title_full Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
title_fullStr Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
title_full_unstemmed Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
title_short Modulation of Bifidobacterium by HD5 during weaning is associated with high abundance in later life
title_sort modulation of bifidobacterium by hd5 during weaning is associated with high abundance in later life
url https://doi.org/10.1038/s43856-025-00977-6
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