Shimizu Yu, Yokoi Yuki, Ohira Shuya, Izumi Hirohisa, Kawakami Satomi, Ihara Miu, Tabata Fuka, Takeda Yasuhiro, Kimura Takashi, Nakamura Koshi, Tamakoshi Akiko, Ayabe Tokiyoshi, Nakamura Kiminori
Innate Immunity Laboratory, Faculty of Advanced Life Science, Hokkaido University, Hokkaido, Japan.
R&D Division, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan.
Commun Med (Lond). 2025 Jul 1;5(1):250. doi: 10.1038/s43856-025-00977-6.
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.
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.
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.
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.
从婴儿期到成年期,肠道中双歧杆菌的定植被认为对我们的健康有益。然而,双歧杆菌属的特定成员如何定植于新生儿肠道,以及生命早期双歧杆菌的定植是否会影响后期富含双歧杆菌的微生物群的建立,这些问题仍未得到解答。小肠潘氏细胞分泌的α-防御素具有选择性杀菌活性,在体外能有效杀死病原体,同时几乎不影响包括双歧杆菌在内的共生菌,从而有助于肠道微生物群的调节。
从日本北海道岩见泽市33名儿童出生后3至5天到3岁期间连续采集148份粪便样本,对母婴进行纵向队列研究(岩见泽微笑研究)。评估微生物群组成以及α-防御素、人防御素5(HD5)的分泌水平,以研究HD5与双歧杆菌定植之间的关系。
我们发现,从断奶前到断奶期,HD5与生命早期双歧杆菌的定植有关。此外,断奶期双歧杆菌的相对丰度较高,这与HD5分泌呈正相关,且与3岁时肠道微生物群成熟时富含双歧杆菌的微生物群的建立有关。
本研究表明,断奶期对于在肠道微生物群中建立与宿主固有免疫和双歧杆菌交织的持久稳态至关重要。