2025-06-05 ユニバーシティ・カレッジ・ロンドン(UCL)
<関連情報>
- https://www.ucl.ac.uk/news/2025/jun/babys-microbiome-protects-against-childhood-viral-infection
- https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00340-9/fulltext
- https://www.nature.com/articles/s41564-024-01804-9
- https://www.nature.com/articles/s41586-019-1560-1
新生児の腸内細菌叢と生後2年間の重症ウイルス性下気道感染症との関連を調査:メタゲノミクスを用いた出生コホート研究 Investigation of associations between the neonatal gut microbiota and severe viral lower respiratory tract infections in the first 2 years of life: a birth cohort study with metagenomics
Cristina Garcia-Mauriño, MD PhD ∙ Yan Shao, PhD ∙ Ada Miltz, PhD ∙ Trevor D Lawley, PhD ∙ Prof Alison Rodger, MBBS PhD ∙ Nigel Field, Prof
The Lancet Published: June 4, 2025
DOI:https://doi.org/10.1016/j.lanmic.2024.101072
Summary
Background
Early-life gut microbiota affects immune system development, including the lung immune response (gut–lung axis). We aimed to investigate whether gut microbiota composition in neonates in the first week of life is associated with hospital admissions for viral lower respiratory tract infections (vLRTIs).
Methods
The Baby Biome Study (BBS) is a prospective birth cohort, which enrolled mother–baby pairs between Jan 1, 2016, and Dec 31, 2017, at three UK hospitals. In the present study, we only included BBS babies with a sequenced first-week stool sample and successful data linkage. Stool was collected in the first week of life for shotgun-metagenomic sequencing. We examined the following microbiota features: alpha diversity (Chao1, Shannon, and Simpson indices) and community structures (cluster-partitioning against medoids method). The participants were followed up through linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) database to determine vLRTI hospital admission incidence in the first 2 years of life. We used Poisson mixed-effects models for univariable and multivariable analyses to evaluate the association between microbiota features and vLRTI hospital admission incidence, adjusting for confounders identified through direct acyclic graphs.
Findings
3305 (95%) of the 3476 BBS-enrolled babies for whom consent to data linkage was obtained were included in the present study. 1111 (34%) babies had a first-week sequenced stool sample, of whom 1082 (97%; 564 born vaginally and 518 born by caesarean section) were successfully linked to HES-APC, and had median follow-up of 2·0 years (IQR 1·4–2·9). Most babies were born at term (996 [92%] ≥37 weeks gestational age and 1070 [99%] >35 weeks gestational age) and healthy (1050 [97%] had no comorbidities), and 520 (48%) were female and 562 (52%) were male. Higher first-week gut microbiota alpha diversity was associated with reduced rates of vLRTI hospital admission (Chao1 Index adjusted hazard ratio [HR] 0·92 [95% CI 0·85–0·99]; Shannon Index adjusted HR 0·57 [0·33–0·98]; and Simpson Index adjusted HR 0·36 [0·11–1·20]). Three microbiota clusters were identified. Cluster 1 had a mixed composition and cluster 2 was dominated by Bifidobacterium breve, with both clusters observed in babies born vaginally and by caesarean section. Cluster 3 was found only in vaginally born babies and was dominated by Bifidobacterium longum. Having cluster 1 (mixed) or cluster 2 (B breve dominated) was independently associated with increased rates of vLRTI hospital admission compared with cluster 3 (B longum dominated; cluster 1 [mixed] 3·05 [1·25–7·41] and cluster 2 [B breve dominated] 2·80 [1·06–7·44]).
Interpretation
We report observational evidence that first-week gut microbiota differences are associated with clinically severe vLRTI in young children. This study identified bacterial species that could be of interest for vLRTI prevention. This finding has important implications for the design of future research and intervention strategies.
Funding
The Wellcome Trust and Wellcome Sanger Institute core funding.
ビフィズス菌の一次継代が新生児腸内細菌叢形成における病原体抵抗性を促進する Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly
Yan Shao,Cristina Garcia-Mauriño,Simon Clare,Nicholas J. R. Dawson,Andre Mu,Anne Adoum,Katherine Harcourt,Junyan Liu,Hilary P. Browne,Mark D. Stares,Alison Rodger,Peter Brocklehurst,Nigel Field & Trevor D. Lawley
Nature Microbiology Published:06 September 2024
DOI:https://doi.org/10.1038/s41564-024-01804-9
Abstract
Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.
帝王切開出産における微生物叢の発育不全と日和見病原体のコロニー形成 Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth
Yan Shao,Samuel C. Forster,Evdokia Tsaliki,Kevin Vervier,Angela Strang,Nandi Simpson,Nitin Kumar,Mark D. Stares,Alison Rodger,Peter Brocklehurst,Nigel Field & Trevor D. Lawley
Nature Published:18 September 2019
DOI:https://doi.org/10.1038/s41586-019-1560-1
Abstract
Immediately after birth, newborn babies experience rapid colonization by microorganisms from their mothers and the surrounding environment1. Diseases in childhood and later in life are potentially mediated by the perturbation of the colonization of the infant gut microbiota2. However, the effects of delivery via caesarean section on the earliest stages of the acquisition and development of the gut microbiota, during the neonatal period (≤1 month), remain controversial3,4. Here we report the disrupted transmission of maternal Bacteroides strains, and high-level colonization by opportunistic pathogens associated with the hospital environment (including Enterococcus, Enterobacter and Klebsiella species), in babies delivered by caesarean section. These effects were also seen, to a lesser extent, in vaginally delivered babies whose mothers underwent antibiotic prophylaxis and in babies who were not breastfed during the neonatal period. We applied longitudinal sampling and whole-genome shotgun metagenomic analysis to 1,679 gut microbiota samples (taken at several time points during the neonatal period, and in infancy) from 596 full-term babies born in UK hospitals; for a subset of these babies, we collected additional matched samples from mothers (175 mothers paired with 178 babies). This analysis demonstrates that the mode of delivery is a significant factor that affects the composition of the gut microbiota throughout the neonatal period, and into infancy. Matched large-scale culturing and whole-genome sequencing of over 800 bacterial strains from these babies identified virulence factors and clinically relevant antimicrobial resistance in opportunistic pathogens that may predispose individuals to opportunistic infections. Our findings highlight the critical role of the local environment in establishing the gut microbiota in very early life, and identify colonization with antimicrobial-resistance-containing opportunistic pathogens as a previously underappreciated risk factor in hospital births.
